bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteosarcoma in patients over 65 years old
Authors: Longhi A. , Errani C. , Ferrari C. , Bertoni F. , Bacchini P. , Mercuri M. , Bacci G. , Picci P. , Ferrari S. 
Published: March 2020

10037 Background: Few data are available in literature about osteosarcoma in patients older than 65.We reviewed the incidence and outcome of osteosarcoma in elderly over 65 in our casistic. Materials and Methods: Patients with high grade osteosarcoma treated in our Institute from 1961 to 2006 aged >65. End point was overall survival (OS). Results: 43 patients aged more than 65 treated for high grade osteosarcoma at our Institute were found: 22 male and 21 females, median age was 69 (range 65–80), 29 had localized disease and 13 were metastatic, 33 had extremity localization and 10 axial, 29 patients had a primitive osteosarcoma and 13 (30%) had a sarcoma in Paget's disease, 1 pt ha post-RT osteosarcoma. Median interval from symptoms to diagnosis was 4 months (0–73) 32 out of 43 received surgery for primitive tumour: 18 had a resection with endoprosthesis, 13 had amputation, 1 pt had palliative surgery, the others received palliative RT, 14 patients received chemotherapy (anthracycline, cisplatin, ifosfamide).2 major complication related to chemotherapy were observed: one toxic death and one septic shock. Twenty-one patients reached a disease free status after surgery. Median OS for all 43 pts was 19 months (SE 3),mean 35 mos (range 3–229), 3 years OS for the all group was 25%. Three years OS (Kaplan-Meyer) for pts with localized disease was 41,5% vs 0% for metastatic pts, 3 yrs OS for pts who had surgery was 30% compared to 0% for those without surgical treatment.Significant prognostic factors (Breslow statistic) were: localized vs metastatic (P<0,004) and surgery vs no surgery (P<0.00005,) The other variables (sex, type of surgery, chemotherapy) were not statistically significant.In another study on patients aged 40–60 with localized osteosarcoma of the extremity we found an OS at 8 years of 62%. Conclusions: Osteosarcoma in this subgroup of elderly is frequently associated to Paget disease and their OS is worse compared to adult of younger age. We need to improve our strategy of treatment to increase the cure rate of these elderly patients. No significant financial relationships to disclose.
Adding cisplatin (CDDP) to imatinib (IM) re-establishes tumor response following secondary resistance to IM in advanced chordoma
Authors: Casali P. G. , Stacchiotti S. , Grosso F. , Messina A. , Crippa F. , Tamborini E. , Bertieri R. , Collini P. , Pilotti S. , Gronchi A. 
Published: March 2020

10038 Background: IM is active in advanced chordoma, possibly by targeting PDGFRB. Secondary progressions following response have been observed. The case of a pt with sacral chordoma and lung adenocarcinoma responding to CDDP soon after stopping IM prompted us to combine the two drugs in IM-resistant advanced chordoma. Methods: Since February 2006, 6 advanced chordoma pts (F=4, M=2; mean age 56 yrs; PS 0–2) with a secondary resistance to IM following previous response, have started IM 400 mg/day + low-dose CDDP (25 mg/sqm/wk) on an individual use basis. Results: One pt completed her treatment (after 7 mos, reaching a total dose of CDDP = 525 mg/sqm), and, following ablation of the residual lesion, is now continuing on IM alone. The remaining pts are on combination therapy (4 for <2 mos). After 4–6 weeks, 4 pts had a PET response (SUV max decrease ≥25%), with subjective improvement and stable disease on CT/MRI, while 2 were metabolically stable. In the 2 pts treated for >12 weeks, a minor dimensional response was observed after 3 mos. The single pt who completed combination therapy had a continuous PET scan improvement throughout treatment, and pre-ablation biopsy of residual tumor showed histological signs of tumor response (marked cellular depletion and sclerohyalinosis in most of the sample, with residual tumor cells intermingled with inflammatory ones). Conclusions: In 4 out of 6 advanced chordoma pts progressing on IM, a tumor response was re-established by adding CDDP, and 2 pts treated for a relatively longer interval showed dimensional tumor shrinkage. Four more pts are starting therapy, and results will be updated. An independent cytotoxic effect of CDDP cannot be ruled out, but sensitivity of chordoma to CDDP is at best occasional. The combination of IM and CDDP may have synergic activity in chordoma. [Table: see text]
Combination chemotherapy with consecutive low-dose cisplatin with ifosfamide and epirubicin (CLD-IEP) in uterine sarcoma
Authors: Murakami F. , Ogawa N. , Yamada M. , Sakurai S. , Ishiya T. , Katase K. , Hasumi K. , Shimizu Y. 
Published: March 2020

10057 Background: To evaluate the efficacy and toxicity of CLD-IEP for patients (pts) with sarcoma uteri. Methods: Eligible criteria were: a histologic proof of advanced or recurrent sarcoma uteri; measurable lesions; age between 18 and 80 yrs; WHO PS 0–3; WBC = 3,000/μL; platelet count = 100,000/μL; hemoglobin level = 9 g/dL; adequate liver function; C-Cr = 40 mL/min; no lung, heart, or brain disease; no previous neoplastic disease; no prior chemotherapy; and informed consent. The CLD-IEP regimen was ifosfamide 700 mg/m2 infused over 2 hrs days 1 through 3; epirubicin 50 mg/m2 bolus day 5; and cisplatin 15 mg/m2 infused over 4 hrs days 1 through 5. The treatment was repeated at 4-week intervals. Results: To date, forty eligible pts (16 leiomyosarcoma [LMS], 4 endometrial stromal sarcoma, and 20 carcinosarcoma) were enrolled in this study and all pts were assessable for response, toxicity, and survival. The median age was 52 yrs (range, 28–77). Thirteen pts received CLD-IEP in the neoadjuvant setting. Nine pts had prior radiotherapy. After a median of 4 cycles (range, 2–13), we observed objective responses in 24 pts (60%), with 5 (13%) CRs and 19 (48%) PRs (95% CI, 42% to 78%, 4% to 22%, 30% to 66%, respectively). Of 16 pts with LMS, 1 CR and 7 PRs (1 pt with good PR surviving more than 48 months after the start of CLD-IEP) were observed. Median overall survival time (MOS) after the start of CLD-IEP for all 40 pts was 17 months (range, 3 to 62). MOS was 20.5 months in the responders versus 9 months in the non-responders (Log-rank, p=0.023). The median progression-free survival time of the responders was 10.5 months. NCI-CTC grade 3 or 4 leucopoenia, neutropenia, thrombocytopenia, and anemia occurred in 63%, 75%, 12%, and 18%, respectively. There was no significant nausea/vomiting, nephrotoxicity, or CNS toxicity. Conclusions: CLD-IEP regimen has significant to moderate anti-tumor activity with acceptable toxicity in pts with sarcoma uteri including LMS. No significant financial relationships to disclose.
Randomized phase II study of trabectedin in patients with liposarcoma and leiomyosarcoma (L-sarcomas) after failure of prior anthracylines (A) and ifosfamide (I)
Authors: Morgan J. A. , Le Cesne A. , Chawla S. , von Mehren M. , Schuetze S. , Casali P. G. , Nieto A. , Elsayed Y. , Izquierdo M. A. , Demetri G. D. ,   Yondelis Sarcoma Study Group
Published: March 2020

10060 Background: Trabectedin, a marine-derived antineoplastic agent, binds to the minor groove of DNA and has previously shown activity in L-sarcomas in single-arm trials. This multicenter, randomized study aimed to characterize the anticancer efficacy with two dosing regimens of trabectedin in pts with treatment-refractory L-sarcomas. Methods: Eligible pts had measurable advanced L-sarcoma, progression despite at least prior A and I, PS 0–1 and adequate organ function. Pts were randomized to IV trabectedin, 1.5 mg/m2, 24h every 3 weeks (q3wk-24h) or 0.58 mg/m2, 3h weekly × 3 on a 28-day cycle (qwk-3h). Primary endpoint is time-to-progression (TTP) and secondary endpoints PFS, overall survival, response, and safety. With 217 events, study provided 90% power to detect a 37% risk reduction in TTP (2-sided 5% significance). Results: 270 pts were randomized as of 5/31/06. Baseline characteristics were comparable: median (range) 2 (1–7) metastatic sites and 2 (1–6) prior regimens; 62% had additional prior agents; 67% had bulky (≥5cm) disease. In the q3wk-24h vs qwk-3h arms median n. cycles were 5 (1–37) vs 2 (1–21); 38% vs 19% received ≥7 cycles. In protocol-specified primary analysis, median (95% CI) TTP was 3.7 (2.1–5.4) vs 2.3 (2.0–3.5) mo [HR: 0.734; p=0.0302] favoring the q3wk-24h arm. Median PFS was 3.3 (2.1–4.6) vs 2.3 (2.0–3.4) mo [HR: 0.755; p=0.0418] and median survival (n=175 events) was 13.8 (12.5–17.9) vs. 11.8 (9.9–13.9) mo [HR: 0.823; p=0.1984]. Benefit from the q3wk-24h arm was more pronounced in pts with central pathology confirmed diagnosis of L-sarcomas. More neutropenia, ↑AST/ALT, emesis and fatigue occurred in the q3wk 24-h. Febrile neutropenia was rare (0.8–1.6%). No cumulative toxicities were noted. Conclusions: Trabectedin can provide clinical benefit to pts with L-sarcoma following failure of all conventional treatment options. Significantly better TTP was noted with the q3wk-24h regimen, although this resulted in somewhat more neutropenia and transaminitis without clinical consequences. No cumulative toxicities were apparent in either arm. Although both dosing regimens are efficacious, there appears to superior disease control with the q3wk-24h arm in this population. [Table: see text]
Effect of early detection of occult brain metastases in HER2-positive breast cancer patients on survival
Authors: Niwinska A. , Tacikowska M. , Lemanska I. , Pienkowski T. , Murawska M. 
Published: March 2020

1015 Aim: The aim of the study was to compare disease free survivals (DFS), survivals from the detection of brain metastases, overall survivals (OS) and the causes of death between two patient groups: group I with disseminated HER2-positive breast cancer and occult brain metastases and group II with symptomatic brain metastases. Material and Methods: MRI screening of the brain was performed in 80 HER2-positive breast cancer pts treated with trastuzumab and cytostatics for visceral metastases. In 29 pts (34%) in whom occult brain metastases were detected, whole brain radiotherapy (WBR) to the brain (30 Gy in 10 fractions) was performed (Group I). They were compared with 48 pts with symptomatic brain metastases treated at the same clinic during the same time period (Group II). Both groups were comparable regarding the site of distant metastases and the type of treatment. All pts in both groups had distant metastases to the lung and/or liver. Results: Median DFS in group I was 17 months and in Group II- 19.9 months (p=0.61). Median survival from dissemination of the disease (visceral metastases) to the detection of occult and symptomatic brain metastases was 9 and 15 months, respectively (p=0.21). Median survival calculated from the detection of brain metastases was 9 and 9.3 months, respectively (p=0.76). Median OS of pts with occult and symptomatic brain metastases was 53.8 and 52 months, respectively (p=0.79). In the group with occult brain metastases 15% of pts died because of progression in the brain and in the group of symptomatic brain metastases the rate of cerebral death was 48%. Conclusions: WBR performed during the asymptomatic period decreased the rate of cerebral deaths, but did not prolong overall survival. Screened MRI of the brain during the asymptomatic period did not improve the outcome of pts with HER2-positive breast cancer and with visceral metastases. No significant financial relationships to disclose.
Quantitative multimarker analysis in circulating tumor cells of patients with breast cancer
Authors: Fersis N. , Koliogiannis D. , Sisic L. , Schlehe B. , Battista M. J. , Sohn C. , Kaul S. 
Published: March 2020

1021 Background: The purpose of this study was clinical application of new methods for quantitative gene expression analysis of circulating tumor cells (CTC) in breast cancer patients. Methods: The high affinity antibodies BM7 (MUC-1) and VU1D9 (EpCAM) were used for immunomagnetic tumor cell enrichment in 10 mL of peripheral EDTA-blood of patients with primary breast cancer (n=167) and metastatic disease (n=131). Separated cells were lysed and used for mRNA isolation and c-DNA synthesis. The breast carcinoma- associated markers MUC1 and EpCAM were determined by conventional RT-PCR. The markers cytokeratin 19 (CK19), mammaglobin 1, survivin, HER-2, CXCR4 and prostate-specific ets factor (PSE) were amplified by real-time quantitative RT-PCR using primers and FAM-labeled TaqMan probes selected with the UniversalProbeLibrary system (Roche AG, Basel, CH). The β-actin transcript served as internal process quality control. Specificity of the RT-PCR was confirmed by examination of blood of healthy donors. Results: Sensitivity for every single transcript was adjusted to 2 tumor cells per 5 ml blood. Tumor-associated transcripts were detected in 31 of 167 (18.5%) patients with primary breast cancer. The marker with the highest incidence of 81% was MUC1. Patients with metastatic disease (n=131) had a positivity rate of 56% and were characterized by multiple marker expression. During a 12 (9–15) months follow-up of 81 patients with primary breast cancer, multimarker positivity was determined in 10 patients, and in three of these patients early metastasis was clinically confirmed. In patients with metastatic disease the CK19 positive CTCs co-expressed either survivin, PSE, CXCR4 or HER2 in more than 70% of the cases. Conclusion: Using a combination of preanalytical immunomagnetic tumor cell enrichment, followed by a multigene quantitative RT- PCR approach, we describe a sensitive detection system for rare circulating breast carcinoma cells. By quantitative expression analysis, survivin, PSE, CXCR4 and HER2 together with CK19 were identified as reliable markers for early detection of metastasis and for prediction of risk of recurrence. The marker panel can be extended further to match patients to best drugs and to predict treatment benefits. No significant financial relationships to disclose.
Differential survival following trastuzumab treatment based on quantitative HER2 expression and HER2:HER2 dimerization in a clinic-based cohort of patients with metastatic breast cancer
Authors: Toi M. , Sperinde J. , Huang W. , Saji S. , Ohno S. , Nakamura S. , Iwata H. , Masuda N. , Aogi K. , Bates M. 
Published: March 2020

1025 Background: Women with metastatic breast cancer (MBC) that overexpress HER2 experience improved overall survival (OS) when treated with trastuzumab. Immunohistochemistry (IHC) for HER2 protein expression and fluorescence in situ hybridization (FISH) for HER2 gene amplification are the preferred methods of determining HER2 positivity. However, not all HER2 positive patients respond equally well to trastuzumab. We describe the identification of subgroups of HER2+ patients with distinct clinical outcomes based on their quantitative levels of HER2 expression and HER2:HER2 dimerization. Methods: 75 patients with MBC drawn from six oncology clinics in Japan were assayed for HER2 expression and HER2:HER2 dimerization using FFPE specimens by the eTag assay, a proximity-based assay designed to detect and quantify protein-protein dimers. All patients had MBC, were treated with at least one chemotherapy (CT) regimen prior to receiving trastuzumab, and had FFPE specimens available for testing. 33% had at least 3 metastatic sites. 88% were selected for treatment based on IHC and 12% based on FISH. 16% were treated with trastuzumab alone and 84% with trastuzumab plus CT. Median clinical follow-up was 26 months. Cox proportional hazards and Kaplan-Meier (KM) analyses were performed. Results: The most significant variables associated with OS were the presence of brain metastases and the total number of metastases. In the overall population, correcting for the confounding influence of number of metastases, KM analyses demonstrated that patients with higher HER2 expression survived significantly longer than patients with lower HER2 expression (HR for death = 0.36, p = 0.0036). This relationship was even more significant for HER2:HER2 dimers (HR = 0.29, p = 0.0003). Conclusions: In a clinic-based population of Japanese women with MBC treated with heterogeneous prior and concomitant (with trastuzumab) CT regimens, the quantitative levels of HER2 expression and HER2:HER2 dimerization identified subsets of patients within a population of pre-selected HER2+ patients with different probabilities of long-term survival following trastuzumab treatment. No significant financial relationships to disclose.
Safety and tolerability of lapatinib in combination with taxanes (T) in patients with breast cancer (BC)
Authors: Crown J. P. , Burris H. A. , Jones S. , Koch K. M. , Fittipaldo A. , Parikh R. , Koehler M. 
Published: March 2020

1027 Background: Lapatinib (L) is an oral, dual ErbB1/B2 tyrosine kinase inhibitor. T are mainstay of BC treatment. The side-effects seen with T in combination with gefitinib and erlotinib include neutropenia, diarrhea and rash. Based on preclinical synergy, early clinical studies with L and paclitaxel (P) or docetaxel (D) were studied. Methods: We summarize pharmacokinetics (PK) and preliminary safety data from 192 patients. Results: PK analysis for EGF10009 (q3w), show systemic exposure was increased for both L (21%) and P (23%) at doses of 1500mg daily and 175mg/m2/q3w, respectively. PK analysis in EGF10021 , (L 1250 mg & D 75 mg/m2 with prophylactic pegfilgrastim) indicated no significant effect on systemic exposure of either agent. Toxicities across all studies include i.e., for all patients = grade 3, neutropenia (7.3%), diarrhea (18.2%), rash (3.6%). The rate of adverse events for neutropenia and rash were similar to each agent alone, however diarrhea was more common. The frequency and severity of diarrhea was increased in studies EGF10009 and EGF102580 where no proactive treatment of diarrhea was introduced, whereas in EGF105764, with proactive treatment, currently no =grade 3 diarrhea has been reported. The data show that the combination of L and P has clinical activity (>70% RR reported in EGF102580). Conclusions: T plus L combinations have a predictable and manageable safety profile and clinical activity of P plus L combination was observed. Proactive diarrhea management is essential for these combinations. Based on the PK data, no dose adjustments are required, and any dose adjustments should be toxicity-based. Ongoing clinical studies investigating the combinations of L with T, and combinations of L with T plus trastuzumab will be reported in the future. [Table: see text] No significant financial relationships to disclose.
Epirubicin (E) cardiac toxicity: A retrospective analysis of 1,097 patients (pts) treated for metastatic breast cancer (MBC)
Authors: Ryberg M. , Nielsen D. L. , Cortese G. , Nielsen G. , Andersen P. K. , Skovsgaard T. 
Published: March 2020

1029 Background: The object of the study was to conduct an analysis and assess a recommended cumulative dose of E corresponding to a 5 % risk for cardiotoxicity taking into account: dose administrations, concurrent risk of dying of MBC and possible predictors of cardiotoxicity. Methods: Data from 1097 consecutive anthracycline naïve pts was retrieved. Pts developing cardiac heart failure according to New York Heart Association (NYHA) Class =II were recorded as having E cardiotoxicity. Statistics: two extended Cox multivariate analysis (events: cardiotoxicity and mortality of MBC) followed by competing risk analysis. Results: 125 pts (11.4%) developed cardiotoxicity. Predictors for increasing the cardiotoxicity hazard ratio (HR) were: 1. cumulative dose of E: as the rate increased with 37% per every 100 mg/m2 E, when given as first line treatment for advanced disease, 2. increasing age as the rate increased with 28.7 % per additional 10 year, 3. x-ray including the heart (HR=2.08), 4. tamoxifen for relapse (HR=1.87), 5. pre-disposition to cardiac disease (HR=3.01). Mortality rate for MBC: the survival was significant lower in pts with increasing tumour burden, poorer performance status, previous adjuvant CMF, and with increasing age. The HR for mortality was significantly increased by increased duration of treatment with E and was highest in the first three months than later on. The risk of cardiotoxicity increased mostly during the first 8 months after cessation of E nearly becoming constant later on. The cumulative dose of E corresponding to a 5 % cardiotoxicity risk was found to be both significantly lower than previously assumed (900 mg/m2) and depend on predictors for mortality and cardiotoxicity. Thus, a pts with no predictors at age 40 the level of 5% risk was 806 mg/m2, at age 50 = 739 mg/m2, at age 60 = 673 mg/m2 and at age 70 = 609 mg/m2. Conclusion: The risk of cardiotoxicity of E was more pronounced than expected and occurred on a much lower cumulative dose of E. Increasing age, x-ray, tamoxifen and pre-disposition to cardiac disease contributed significantly to this. No significant financial relationships to disclose.
A phase II trial of capecitabine (C) in combination with the farnesyltransferase (FT) inhibitor (FTI), tipifarnib (T), in patients (pt) with metastatic breast cancer (MBC): ECOG trial 1103
Authors: Wang M. , Gradishar W. J. , Sparano J. A. , Perez E. A. , Sledge G. 
Published: March 2020

1036 Background: Approximately 30% of human cancers have mutated Ras genes that produce proteins that remain in an active state causing uncontrolled proliferative signals. Post-translational modification of Ras include farneyslation catalyzed by FT. Tipifarnib (R115777) is an oral FTI active against human tumor cell lines and exhibiting modest single agent activity in pts with previously treated MBC. A previous phase I trial reported that CT inhibited farneyslation in peripheral blood mononuclear cells without affecting the pharmacokinetics of either agent. Objective: To evaluate objective response rate (ORR) of CT in taxane refractory MBC and to secondarily evaluate associated toxicity and progression-free survival (PFS). Methods: Pt with measurable MBC, previously treated (rx) with an anthracycline and relapse on a taxane or within 30 days (d). Study rx: T- 300 mg, po BID × 14 d plus C- 1,000 mg/m2, po BID × 14 d, followed by 7 d rest. Tumor reassessment was repeated q 3 cycles. The study was designed to detect improvement in ORR from 25% with C alone to 40% for the CT combination (90.5% power; type I error rate of 9.9%; 21 responses in 64 eligible pt needed to be promising. Results: 66/71 pt are available for primary analysis. Median age 50 yrs. Performance status: 0–1, 100%. ORR: PR-4.8% (3/62) [95% CI 0.01, 0.13], SD - 21% (13/62) [ 95% CI 0.12, 0.33]. Median survival - 10.6 months. Toxicity (%): anemia - 8(G3/4), neutropenia - 30 (G3/4), thrombocytopenia - 8 (G3/4), HFS-8 (G3), nausea/vomiting - 11(G3), diarrhea - 8 (G3), sensory neuropathy - 5 (G3). Conclusion: CT in taxane -refractory MBC has low antitumor activity without excessive toxicity. More mature data, including PFS, will be presented. No significant financial relationships to disclose.