bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful treatment with minimal chemotherapy followed by low-dose involved field radiotherapy in children with Hodgkin's disease: A 20-year experience in a single institution in Greece
Authors: Pourtsidis A. G. , Doganis D. , Baka M. , Bouhoutsou D. , Varvoutsi M. , Servitzoglou M. , Kosmidis S. , Synodinou M. , Strantzia C. , Kosmidis H. 
Published: August 2020

10052 Background: The vast majority of children with Hodgkin's disease (HD) nowadays have an excellent chance of definite cure. The high curative rates as well as the prevention of late effects have to be among aims when managing children with HD. The purpose of our retrospective study was to report the outcome and prognostic factors of patients (pts) less than 15 years of age with HD treated with chemotherapy (CT) followed by low dose radiation from 1987 to 2006. Methods: We studied 58 children analyzing the following data: age, sex, stage, histology, therapy correlating these with the outcome of pts. Among 35 boys and 23 girls, age at diagnosis 4.5 - 15 years (median 12), all aged 7 years or less were boys (8/58). Nodurar sclerosis was the predominant histology subtype (69%) and 45% had advanced disease (stages III or IV). According the study period pts with early stage received 4 cycles of ABVD or VBVP and those with advanced stage disease alternating 3 cycles of MOPP/ABVD or 2 of MOPP/ABVP for stage III and alternating 3 cycles of MOPP/ABVD or 2 OPPA plus 4 COPP for stage IV. All pts had a good response (more than a 70% reduction) after initial CT and received 20 Gy of RT to initially involved fields. Results: Complete remission (CR) was achieved in all patients. Chemo- and radio-therapy were well tolerated. Fifty-three pts (DFS: 91.4%) live in their first complete remission. In 5 pts (8.6 %) relapse occurred, 20 -65 months from dx (median 25 mo). All received salvage treatment in combination with high dose CT and autologous stem-cell transplantation (SCT). Of the 5 relapsed all live 21 - 207 months (median 75 mo) from the dx of relapse and 41 - 232 mo (median 99) from the dx of disease. Second (thyroid cancer) plus third malignancy in one (osteosarcoma) was detected in 3 pts and all are alive. Finally for our group the overall survival is 100% and all children are alive 25 - 264 mo from dx (median 145 mo) and the event free survival is 86.2% (50/58). No factors related to the outcome were detected. Conclusions: In conclusion combined-modality therapy remains the standard of care for children with HD. However, there may be a significant number who can be cured with chemotherapy alone. At this moment the main question is: who can be cured without RT? No significant financial relationships to disclose.
Treatment of relapsed/refractory pediatric sarcomas with gemcitabine and docetaxel
Authors: Cruz O. , Mora J. , Parareda A. , de Torres C. 
Published: August 2020

10059 Background: Cure rates for children andadolescent's cancer have improved steadily for most tumor types. However, recurrent disease or progressive-refractory sarcomas remain incurable and most of these patients die within 1 to 2 years after diagnosis. In this report we describe experience with gemcitabine-docetaxel (G+D) in pediatric patients with relapsed or refractory sarcomas. Methods: Ten relapsed/refractory pediatric sarcoma patients including 6 Ewing sarcoma, 2 synovial sarcoma, 1 osteosarcoma, and 1 undifferentiated sarcoma were treated in an outpatient setting with gemcitabine 1000 mg/m2 over 90 minutes on day 1 and 8, and docetaxel 100 mg/m2 ver 3 to 4 hours on day 8 of a 21-day cycle, as an investigational rescue therapy. Results: A median of 7 cycles were given per patient (range, 4 to 10), and a total of 70 cycles were administered. To date, 2 patients continue on treatment. All symptomatic patients responded clinically to this regimen. No grade 3–4 toxicities were encountered. Five patients (50%) had a CR/functional CR, 4 patients (40%) had a PR/SD, and 2 patients (20%) had PD, which provides an overall response rate (CR+PR/SD) of 90%. Prolonged disease stabilization was achieved even for multiple relapsed patients with the G + D regimen, median duration of responses 11 months. Five out of the 10 patients (50%) are alive, median follow-up 48 months from diagnosis. Conclusions: The G + D regimen seems to be active against advanced pediatric sarcomas. It does not exacerbate pre-existing toxicities and allows good quality of life. Evaluation in a large, formal phase II trial for ES patients is ongoing. No significant financial relationships to disclose.
Progression-free survival (PFS) of patients with HER2-negative, estrogen-receptor (ER)-low metastatic breast cancer (MBC) with the addition of lapatinib to letrozole: Biomarker results of EGF30008
Authors: Finn R. S. , Press M. , Dering J. , Florance A. , Platek G. , Arbushites M. , Koehler M. , Johnston S. 
Published: August 2020

1018 Background: Lapatinib (Lap), an oral, dual inhibitor of EGFR/HER-2, is approved with capecitabine for treatment of HER-2+ MBC for recurrence after taxane, anthracycline, and trastuzumab-based therapy. Letrozole (Let) has activity in hormone-receptor positive (HR+) BC. It has been hypothesized that peptide growth factor signaling and hormone signaling pathways interact and dual targeting of these pathways results in therapeutic synergy. We report a blinded analysis of HER-2, ER, and progesterone receptor (PR) expression for patients (pts) with HR+ MBC at first diagnosis or post-adjuvant relapse and response to Lap + Let versus Let. Methods: 1286 pts were randomized 1:1 to 2.5 mg Let daily plus either 1500 mg Lap daily or placebo. The primary endpoint was PFS in HR+, HER-2+ MBC pts; secondary endpoints included PFS in the intent-to-treat population. Blinded, centralized commerical laboratory analysis of archived tumor tissue for HER-2 (IHC and/or FISH) and academic laboratory semi-quantitative analysis of ER/PR (IHC, H-score) was performed and correlated with clinical outcome. Results: In 219/1286 (17%) HER-2+ (FISH+ or IHC3+) pts, a significant improvement in median PFS was observed for Lap + Let versus Let (8.2 v 3.0 mos, HR = 0.71, 95% CI 0.53, 0.96, p = 0.019). No significant difference in median PFS was seen in 952 (74%) HER-2-negative pts (13.4 v 13.7 mos, HR = 0.90, 95% CI 0.77, 1.05, p = 0.188). 821/952 (86%) HER-2-negative pts had tissue available for quantitative ER and PR analysis. Analysis of ER and PR by quartile identified a subgroup of HER-2-negative pts that benefitted from adding Lap to Let. Pts with the lowest quartile of ER expression (H-score <160, n = 207) had a significant improvement in median PFS (13.6 mos v 6.6 mos, HR = 0.65, 95% CI 0.47, 0.9, p < 0.005). Pts with higher levels of ER did not significantly benefit from adding Lap to Let. Analysis of PR expression did not identfiy a subgroup that benefited from Lap. Conclusions: Pts with HER-2-negative, ER+ MBC and low ER expression may benefit from the addition of lap to let. Additional analyses of EGFR, other biomarkers, and prior hormone therapy will be presented. [Table: see text]
N0337: Phase II study of capecitabine in combination with vinorelbine and trastuzumab for the first or second treatment of HER2+ metastatic breast cancer
Authors: Tan W. , Allred J. , Salim M. , Flynn P. , Kugler J. W. , Stella P. J. , Wiesenfeld M. , Bernath A. M. , Fitch T. R. , Perez E. A. 
Published: August 2020

1020 Background: Trastuzumab-containing regimes have dramatically improved outcome of patients with HER2+ breast cancer. Efforts to improve efficacy and tolerability of combination regimens with this monoclonal antibody are important for patient care. Thus, we conducted a multi-institutional phase II study of a triplet combination in patients eligible to receive either first- or second-line treatment for HER2+ metastatic breast cancer (MBC). Methods: A phase II study designed to test that the true confirmed response rate (CRR) was at most 45% versus a true CRR of at least 65% was done (March 2005-June 2008). This design required that at least 25/45 confirmed responses in evaluable patients for the treatment to be considered promising. Patients received capecitabine 825 mg/m2 po (days 1–14), vinorelbine intravenously (IV) 25 mg/m2 days 1 and 8 every 3 weeks and trastuzumab IV 8mg/kg day 1, week 1, and then 6 mg/kg q 3 weeks. Tissue and blood have been collected for future studies on biomarkers. Results: 47 women were accrued, one patient cancelled participation prior to receiving any study drug, and another had a major protocol violation. 45 patients were evaluable and 30 (67%) achieved a confirmed response, (26 patients, 58% had a confirmed partial response and 4 patients, 9% had a confrimed complete response). Median progression free survival was 11.3 months (95% CI 8.4–23.2 months), median overall survival was 27.2 months (95% CI: 26.6-NA months), and among the 30 responders, the median duration of response time was 15.5 months (95% 7.7–26.1 months). The most common grade 3 events include neutropenia 61%, fatigue 13%, skin reaction-hand-foot 11%, and leukopenia 11%. Alopecia was not noted with this regimen. Conclusions: This triplet combination is effective, safe, and is promising in patients with HER2+ MBC. A phase III study should be conducted to compare the best doublet with this triplet combination whether this would lead to better clinical outcomes. [Table: see text]
Bevacizumab and oral chemotherapy for patients with lymphangitic breast cancer: A phase II randomized study of bevacizumab with sequential versus concurrent oral vinorelbine plus capecitabine
Authors: Locatelli M. A. , Curigliano G. , Fumagalli L. , Ghisini R. , Mancuso P. , Bertolini F. , Viale G. , Lunghi L. , Goldhirsch A. 
Published: August 2020

1031 Background: Antiangiogenic agents are most likely to be effective in patients (pts) with an extensive cutaneous neo-angiogenic trait of disease. There is a compelling need to monitor the biological activity of such agents and identify markers of efficacy. Methods: We evaluated the activity and biological effects of bevacizumab (B) (15 mg/kg, iv q 3 weeks) in a phase II randomized trial in pts with locally advanced breast cancer (BC) with lymphangitic spread to the chest wall. Primary aim was to assess activity and toxicity of B administered alone followed by sequential oral vinorelbine (V) plus capecitabine (C) (arm A) or with concurrent V plus C (arm B). Secondary aim was to evaluate predictive role of circulating progenitor cells (CECs) and progenitor endothelial cells (CEPs) as surrogate markers of antiangiogenic activity. We collected blood samples of all pts at baseline, at day 12, 42, and at progression. Results: Planned accrual was of 43 pts of whom 23 were enrolled (9 pts in arm A; 14 pts in arm B). Median age was 51 years (range 35–68). Most of the pts had a “triple negative” phenotype [19/23 (82%)]. 10/23 pts (43%) received ≥ 2 previous lines of chemotherapy. 19 pts (82 %) are evaluable for response and all 23 pts are evaluable for toxicity. We observed 5 PR (45%) and 6 SD (55%) in arm B. In arm A, while on B alone, 6 (75%) of the pts had PD and 2 (25%) had a short term SD. Adding VC to B 2 PR (25%), 3 SD (37.5%), and 3 PD (37.5%) were observed. Toxicity profile was typical for use of B (hypertension). The absolute mean number of CECs was 158/ml (range 45–461) (n = 23) at baseline, 116/ml at +12 (range 47–275), and 194/ml at +42 (range 36–891). Mean absolute value of CEPs was 270 (range 28–1060) at baseline, 245/ml at D+12 (range 14–981), and 143/ml (range 5–610) at D+42. The fraction of apoptotic/necrotic CECs was 54±19% at baseline, 64±21 at+12, and 52±18 at+42. Conclusions: Preliminary data showed that B alone is not an effective treatment in pts with lymphangitic spread of BC to the chest wall. Additional data on CECs and CEPs are needed to clarify their potential usefulness as a surrogate markers of antiangiogenic activity of B-based regimen. No significant financial relationships to disclose.
Gene expression differences between disseminated tumor cells and tumor cells from overt bone metastases in patients with metastatic breast cancer
Authors: Broom R. J. , Amir E. , Cawthorn T. , Freedman O. , Gianfelice D. , Barth D. , Galica J. , Wang D. , Done S. J. , Clemons M. 
Published: August 2020

1040 Background: Despite extensive work evaluating molecular differences between primary tumors, circulating tumor cells, disseminated tumor cells (DTCs) and established metastases, it is not apparent which genetic alterations are required to form viable, independent bone metastases (BM). A major limitation in exploring the genetic differences between DTCs and established BM is the paucity of fresh BM tissue available. Methods: Ten breast cancer patients with BM underwent a CT-guided BM biopsy and a bone marrow aspiration (for DTCs). Tumor cells were enriched by immunomagnetic separation and RNA was extracted from each sample. Gene expression profiling was conducted using Illumina Human Ref-8 bead arrays. Microarray data was analyzed using BeadStudio software to identify differentially expressed genes. Ingenuity Pathway Analysis software was used to identify genes integral to specific pathways involved in tumor dissemination. Results: The yield of analyzable malignant cells from BM and bone marrow aspirates was 60% and 80%, respectively. A signature of 133 genes was identified that was differentially expressed between the two sample types. Paired analysis of samples from the same patients identified a subset of 161 genes, of which 52 overlapped with the initial unmatched signature. Several genes relevant to breast cancer metastasis to bone (i.e., osteopontin, CTGF, parathyroid hormone receptor, EGFR) were significantly over-expressed in the BM compared to the DTCs. Conclusions: Results suggest that there are specific subsets of genes, which are required for DTCs in the bone marrow to form overt BM. A number of genes identified are already known to participate in osteolytic BM formation. This signature may allow identification of patients at increased risk for developing BM. No significant financial relationships to disclose.
Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: A multivariate analysis of the French Sarcoma Group database
Authors: Italiano A. , Delva F. , Brouste V. , Terrier P. , Trassard M. , Michels J. , Collin F. , Coindre J. , Blay J. , Bui B. 
Published: August 2020

10504 Background: The SMAC meta-analysis failed to demonstrate that adjuvant chemotherapy (AC) significantly improves overall survival (OS) in adult patients with localised resectable soft-tissue sarcoma (STS). We report here the analysis of the impact of AC in the population of STS patients included in the prospective database of the French Sarcoma Group. Methods: Between 1980 and 1999, 2,029 pts with STS were admitted to one of the 20 tertiary cancer centers of the GSF for the management of a first tumoral event and were included prospectively in a comprehensive database. 152 pts were excluded from the study because of metastatic disease at diagnosis. All the cases were reviewed by the pathology subcommittee of the GSF. Tumor grade was assessed according to the FNCLCC system based on tumor differentiation, mitotic count, and necrosis. Results: 283 pts (14.5%) had grade 1, 736 (39.5%) grade 2 and 858 (46%) grade 3 tumors. 1,102 pts (59%) had extremity tumors. The commonest pathological subtypes were MFH 22.5%, liposarcoma 18%, leiomyosarcoma 13%, and synovial sarcoma 10%. 1,122 pts (60%) received adjuvant radiotherapy. AC was delivered in 16 grade 1 pts (6%), 167 grade 2 pts (23%) and 323 grade 3 pts (38%). The majority of patients who received AC had tumors with a deep topography (91%) and/or > 5 cm (75%) and/or located in the limbs (61%). The median follow-up was 9 years. The 5 year-OS was 90% for grade 1 pts, 63% for grade 2 pts and 46% for grade 3 pts. On multivariate analysis ( table 1 ), AC was strongly associated with improved metastasis-free survival (MFS) (5 year MFS: 53% vs 47%, HR 0.7 [0.5–0.9], p=0.003) and overall survival (OS) (5 year OS: 56% vs 44%, HR 0.7 [0.5–0.8], p=0.004) in grade 3 pts. This association was not observed in grade 2 pts (5 year MFS: 73% vs 72%, HR 0.9 [0.6–1.4], p=0.9; 5 year OS: 73% vs 65%, HR 0.7 [0.5–1.1]). Conclusions: This large cohort-based analysis with long-term follow-up indicates that FNCLCC grade 3 pts are likely to benefit from AC. [Table: see text] [Table: see text]
Treatment of aggressive fibromatosis with pegylated liposomal doxorubicin: The Royal Marsden Hospital experience
Authors: Constantinidou A. , Scurr M. , Jones R. , Al-Muderis O. , Judson I. 
Published: August 2020

10519 Background: Aggressive fibromatosis (AF) or desmoid tumors are monoclonal proliferations which are locally invasive but do not metastasise. Sporadic tumors are usually associated with mutations in the beta-catenin gene CTNNB1whereas those occurring in the context of familial adenomatous polyposis usually have inactivating mutations in APC. Histologically they are characterised by nuclear expression of beta-catenin. When surgery and radiotherapy are not applicable or fail to control the disease, systemic treatment with anti-oestrogens, non steroidal anti-inflammatory drugs (NSAIDs) and chemotherapy can be used. A variety of regimens are reported to have activity including methotrexate/vinblastine and doxorubicin/dacarbazine. Recent reports indicate that single agent pegylated liposomal doxorubicin (Caelyx, C) is also effective. Methods: Ten patients with AF received C between June 2006 and December 2008. C was administered intravenously at 50 mg/m2 over 1 hour every 4 weeks. Results: The female/male ratio was 9:1 and the median age at presentation was 39.5 years (range 18–53). All patients had progressive fibromatosis. Fifty percent had previously been treated with surgery/radiotherapy or both. All but one had previous systemic therapy which comprised tamoxifen/toremifene (6), NSAIDs (1), chemotherapy (1) and imatinib (1). C was well tolerated with mucositis (6/10), palmar-plantar erythema (4/10) and fatigue (2/10) being the main toxicities. A dose reduction to 40 mg/m2 was required in 50% of cases hence the optimal dose lies between 40 and 50 mg/m2. One patient is currently receiving treatment and is too early to assess. For the nine patients who have completed treatment the median number of C cycles was 6 (range 4–6). Objective response according to RECIST was achieved in 4/10 patients and in 5 patients the best response was stable disease. Clinical benefit (pain relief, improved mobility) was observed in all patients. The duration of response ranged from 4 to 28 months. Conclusions: This is the largest series of patients with AF receiving C presented to date. C as single agent therapy has acceptable toxicity and highly promising activity in unresectable AF and may provide long term clinical benefit in some patients. No significant financial relationships to disclose.
An open-label multicenter phase II study of bevacizumab for the treatment of angiosarcoma
Authors: Agulnik M. , Okuno S. H. , Von Mehren M. , Jovanovic B. , Brockstein B. , Benjamin R. S. , Evens A. M. 
Published: August 2020

10522 Background: The limited therapeutic options and dismal prognosis for patients (pts) with angiosarcomas (AS) provide a strong rationale for the evaluation of new therapies. Preclinical studies in AS tumor models have shown antitumor effects of antiangiogenic agents. We conducted a phase II study to determine the antitumor effect of bevacizumab in AS. Methods: The study was a two-stage design in which patients with newly diagnosed or relapsed/refractory AS and epithelioid hemangioendotheliomas were treated with bevacizumab 15 mg/kg IV every 3 weeks. Treatment was continued until progression or unacceptable toxicity. Response was assessed by RECIST criteria. Results: To date, of 29 pts enrolled, 28 received treatment. Baseline data on 29 pts are: M:F= 12:17 and median age 62 (range 18–94). Three pts are not evaluable (1 too early, 2 full treatment not given). Among 26 pts evaluable for response so far: 3 have PR (range 3–16 cycles), 13 have SD (3–32 cycles) and 10 have PD. ORR 3/26 (12%). After 141 cycles of therapy, only 1 grade 4 adverse event occurred (thrombocytopenia) and 5 patients experienced a grade 3 adverse event (anemia, pleural effusion, congestive heart failure, pain, headache, and nausea). Conclusions: Bevacizumab monotherapy for AS resulted in a response rate of 12% and tumor stabilization achieved by 62% of pts. Further studies with bevacizumab in combination with chemotherapy should be explored in this disease. No significant financial relationships to disclose.
Phase II study of gemcitabine and docetaxel as first-line chemotherapy in locally advanced/metastatic leiomyosarcoma
Authors: Seddon B. M. , Scurr M. R. , Jones R. L. , Wood Z. , Propert-Lewis C. , A'Hern R. , Whelan J. S. , Judson I. R. 
Published: August 2020

10528 Background: Locally advanced/metastatic soft tissue sarcoma is invariably incurable with a poor prognosis. Recently gemcitabine and docetaxel have been shown to be active in pre-treated relapsed leiomyosarcoma. This study aims to investigate the combination as first line treatment in patients with unresectable incurable leiomyosarcoma. Methods: Patients received gemcitabine 900mg/m2 days 1 and 8, and docetaxel 100mg/m2 day 8, administered 3-weekly for up to 8 cycles, with GCSF support on days 9–15. Patients who had received previous radiotherapy were treated at 75% dose. Patients were evaluated for response by RECIST after cycles 2, 4, 6, and 8, and three-monthly after completing treatment. The study was conducted with a Simon 2-stage design, recruiting 19 patients in stage 1, and 25 patients in stage 2. The primary endpoint was response rate, and secondary endpoints progression free survival (PFS), overall survival (OS), and toxicity evaluation. Results: Forty-four patients were treated. Eligible patients had histologically proven leiomyosarcoma of the uterus (48.9%) or other sites (51.1%) unresectable for cure, with measurable disease, no previous chemotherapy, adequate organ function, and performance status 0–2. 84.4% had metastatic disease, and 15.6% had locally advanced disease. 11% of patients had grade 1 disease, and 89% had grade 2/3 disease. All patients had demonstrated disease progression prior to trial entry. Responses were as follows: partial response 12 (27%), stable disease (confirmed) 16 (36%), stable disease (unconfirmed) 5 (11%), progressive disease 11 (25%). Median OS and PFS were 578 (95% CI 131–322) and 216 (95% CI 24–169) days. Progression free rates at 3 and 6 months were 68.9% (95% CI 55.1–82.7%) and 57.8% (95% CI 43.1–72.5%). Conclusions: This study demonstrates gemcitabine and docetaxel to be active in leiomyosarcoma in the first line setting. Further investigation comparing the combination with current standard therapies for leiomyosarcoma is warranted. No significant financial relationships to disclose.