bluuebunny/crossref_metadata_2025_split huggingface dataset:
Levetiracetam for the treatment of hot flashes: A pilot study
Authors: Thompson S. L. , Bardia A. , Tan A. , Barton D. , Kottschade L. , Sloan J. , Christensen B. , Smith D. , Loprinzi C. 
Published: March 2020

9116 Background: Hot flashes affect 75 % to 90 % of women transitioning to menopause and are a major cause of morbidity among breast cancer survivors. Levetiracetam, a popular anticonvulsant, is a centrally active agent that anecdotally appeared to reduce hot flashes in clinical practice. This phase II trial sought to evaluate the efficacy of levetiracetam in reducing hot flashes among women with a history of breast cancer or women who did not wish to take estrogen therapy for fear of an increased risk of breast cancer. Methods: Women who were experiencing bothersome hot flashes (≥ 14 times per week, for ≥ 1 month) were eligible. A single arm pilot study design based on previous work was used with a planned sample size of 30 patients. The patients did not receive any study medication during the first week (baseline week). At the beginning of the second week, patients were started on levetiracetam (500 mg), and were to increase the dose by 500 mg each week to a goal of 1,000 mg twice daily. Hot flash diaries were completed daily. The primary endpoint was hot flash score (frequency times average severity). The change from week 1 (baseline) to week 5, the last treatment week, was analyzed by paired t-test and related Wilcoxon procedures. Results: A total of 30 women were enrolled onto this study in eight months. All patients were eligible. 19 women completed all 4 weeks of the study treatment and provided complete data. After treatment with levetiracetam for 4 weeks, mean hot flash scores were reduced by 57% (95% CI 39%-75%), while mean hot flash frequencies were reduced by 53% (95% CI 38%-68%), reductions being greater than what would be expected with a placebo. There were significant improvements, compared to baseline week data, in sweating, hot flash distress, and satisfaction with hot flash control. Eight subjects stopped the study drug due to treatment related adverse events (grade I/II), with the most frequently reported being somnolence, fatigue and dizziness. Conclusions: While levetiracetam appears to be a promising therapy for the treatment of hot flashes, further study is needed to better substantiate the toxicity and efficacy of this drug before it can be more definitively recommended for use in clinical practice. No significant financial relationships to disclose.
Renal insufficiency in bone metastasis cancer patients: Prevalence and implications on anticancer drugs management, subgroup analysis of the IRMA study
Authors: Janus N. , Le Tourneau C. , Launay-Vacher V. , Gligorov J. , Rixe O. , Pourrat X. , Beuzeboc P. , Morere J. , Deray G. , Oudard S. 
Published: March 2020

9121 Background: The IRMA study reported the high prevalence of renal insufficiency (RI) in 4684 solid tumour patients, with a glomerular filtration rate (GFR) <90 ml/min for 50–60%. Furthermore, 80.1% were receiving nephrotoxic anticancer drugs and 79.9% drugs necessitating dosage adjustment. We present the results for IRMA patients with bone metastasis (BM). Methods: Subgroup analysis of IRMA patients with BM. Data collected: sex, age, weight, serum creatinine (SCR), bone metastasis (BM) and anticancer drugs. The prevalence of SCR>110 μmol/L was assessed. GFR was estimated with Cockcroft-Gault (CG) and abbreviated MDRD (aMDRD) formulae. Drugs necessitating dosage adjustment and those potentially nephrotoxic were identified. Chi-square test was used to compare the prevalence of RI between patients with BM and patients without, for all patients and for breast cancer (BC) ones. Results: 1,000 patients (BC 577) with BM were included: median age 60, mean 59.8, weight 66 kg, 659 women. The prevalence of SCR>110 μmol/L was 8.3%. That of GFR<90 ml/min was 57.9% with CG and 54.7% with aMDRD. 83.4% of treated patients received at least one drug needing dosage adjustment (or no data) and 69% received at least one nephrotoxic drug. The prevalence of RI was not statistically different between patients with or without BM. However, the prevalence of RI was significantly higher in BC patients with BM as compared to BC patients without BM (62.1 versus 56.7 %, p=0.04). Conclusions: RI is highly frequent in cancer patients with BM. Appropriate evaluation of renal function necessitates CG or aMDRD calculation. In those patients, and especially in breast cancer patients with BM, anticancer drugs should be cautiously selected regarding their potential renal toxicity and need for dosage adjustment. [Table: see text] No significant financial relationships to disclose.
Risk assessment model for first-cycle chemotherapy-induced neutropenia (CIN) among lung cancer (LC) patients: DELFOS study
Authors: Rifà J. , González Larriba J. L. , Casas Fernández de Tejerina A. , López Pousa A. , Febrer L. , Carrato A. 
Published: March 2020

9132 Background: CIN is common in LC patients (pts) who receive myelosuppressive chemotherapy and contributes to therapy induced morbidity and mortality therefore having strong impact both on health and on health care systems. The objective of the present research study is to determine a predictive model for first-cycle CIN in pts with LC in Spain. This will help to establish appropriate protocols in routine patient care, hence improving clinical decision making. Methods: Data were obtained from the DELFOS Study, a multicentre non-interventional prospective-cohort study in Spain. This study has completed enrolment and data are available for this planned analysis. To obtain the predictive logistic regression model (LRM), the hierarchical principle was followed as a way to enable results replication. The model was implemented for CIN defined as neutropenia grade = 3 (with or without body temperature = 38 C°). A receiver operating characteristics (ROC) Curve was used to determine the model's sensitivity and specificity. Results: A total of 210 pts with LC (86 % male; mean age: 63 yrs (SD: 10); ECOG = 2;) were included in 65 Spanish medical oncology health centres. A selection process of potentially relevant factors was performed among socio-demographic, clinical and biochemical parameters collected. The LRM obtained predicted the CIN at first-cycle (pChi-sq < 0.0005) through the following factors: baseline platelet count (BPC), baseline haemoglobin (Hb) and type of chemotherapy treatment. In that sense, lower BPC was associated with higher risk of CIN (p<0.0005; OR=1.01; 95%CI (1.005, 1.016)) and the same happened with lower baseline Hb (p=0.017; OR=1.4; 95%CI (1.06, 1.8)). Pts in Platinum-based Chemotherapy showed higher risk of CIN compared to those in combination of Platinum and Taxane-based Chemotherapy (p=0.027; OR=5.5; 95%CI (1.2, 24.9). Inherent sensitivity and specificity of the equation were, respectively, 70.4% and 73.2%. Conclusions: A statistically significant risk predictive model for first-cycle CIN in pts with LC in Spain was implemented. Three predictive factors were identified. Baseline platelet count and baseline Hb were inversely associated with toxicity. Toxicity increased for pts with Platinum-based Chemotherapy regimens. No significant financial relationships to disclose.
A phase II randomized, placebo-controlled, double-blind study of the efficacy and safety of RC-1291 (RC) for the treatment of cancer cachexia
Authors: Garcia J. , Boccia R. V. , Graham C. , Kumor K. , Polvino W. 
Published: March 2020

9133 Background: Cancer cachexia is closely correlated with poor outcome and poor survival. RC is an oral ghrelin mimetic with orexigenic and anabolic activity. Methods: A phase II trial enrolled 81 patients with cancer, performance scores of 0–2, and weight loss of 5% or more within 6 months prior to enrollment at 17 sites in the US. Patients were randomized to treatment with two placebo (PL) or two 25 mg RC capsules taken once daily for 12 weeks. Outcome measures included lean body mass (LBM), total body mass (TBM) by DEXA (central reading), scale weight, handgrip strength (HS) and QOL measures. Biochemical markers included IGF-1 and IGFBP-3. In the per protocol analysis (32 RC, 28 PL) more than 20 cancer types were represented; the most common were lung (n=13) and colorectal cancer (n=15). The two treatment groups were balanced at baseline except for (RC vs PL, respectively): gender (66 % male vs 57 %), TBM (60.9 kg vs 65.3 kg), and HS (53.8 kg vs 56.6 kg). The analyses (repeated measures ANOVA without imputation) included all available data from the patients. Results: TBM and LBM (primary endpoint at 8 wks) were significantly increased vs. PL at wks 4 and 8 and at wks 4, respectively. The magnitude of the increase vs. baseline was stable from wk 4 through wk 12 during RC treatment for both TBM and LBM. HS was increased at significantly at wk 8. IGF-1 and IGFBP-3 significantly increased at wks 4, 8, and 12. No significant differences were found on the QOL or scale weight measures. RC was well tolerated. Patients having any AEs were 96% vs 87% and SAEs were 32% and 26% for RC and PL, respectively. The percent of patients and types of AEs were similar; possible exceptions included cardiac events and infections (11% vs 3% and 30% vs 42%, RC vs PL, respectively). Conclusions: In this randomized, double-blind, placebo-controlled trial, RC treatment led to improvements in LBM, TBM and HS. RC-1291 is a promising potential therapeutic agent for the treatment of cancer cachexia. No significant financial relationships to disclose.
Update on the development of the international neuroblastoma risk group (INRG) classification schema
Authors: Cohn S. L. , London W. B. , Monclair T. , Matthay K. K. , Ambros P. F. , Pearson A. D. 
Published: March 2020

9503 Background: Modern treatment strategies for neuroblastoma (NB) are tailored according to patient risk. However, it is not currently possible to compare the results of clinical studies conducted around the globe because the criteria used to define risk are not uniform. A committee of international investigators with expertise in NB have worked during the past 2 years to develop a uniform International NB Risk Group (INRG) Classification System for pre-treatment stratification. Methods: Investigators from North America and Australia (COG); Europe (SIOPEN and Germany), and Japan collated data on 8,800 children with NB diagnosed between 1990 and 2002. Survival tree regression analyses tested 13 potential prognostic factors. Tumor differentiation, MKI, and diagnostic category were evaluated individually in lieu of the International NB Pathology Classification (INPC) system to determine if these histologic features had prognostic value independent from age. To stage patients at the time of diagnosis prior to surgery, a new staging system was developed (INRGSS) based on the presence or absence of image-defined risk factors (IDRFs) and metastases. Results: Since statistical analyses demonstrated support for an optimal age cut- off between 14–19 months, 18 months was selected. In addition to age, stage, MYCN amplification, tumor differentiation, ploidy, and genetic aberrations of 11q were found to be the most highly prognostically significant factors. These clinical and biological factors were combined to define 15 INRG pre-treatment groups. Patients with low- (3 groups), intermediate- (4 groups), high- (4 groups), or ultra-high-risk NB (4 groups) had EFS of ≥85%, >70–85%, >50–70%, or <50%, respectively. Conclusion: International collaborative studies in NB will be greatly facilitated by the INRG classification system which will allow comparisons of different risk-based therapeutic approaches in homogeneous patient cohorts. No significant financial relationships to disclose.
Response and toxicity to a dose-intensive multi-agent chemotherapy induction regimen for high risk neuroblastoma (HR-NB): A Children's Oncology Group (COG A3973) study
Authors: Kreissman S. G. , Villablanca J. G. , Diller L. , London W. B. , Maris J. M. , Park J. R. , Reynolds C. P. , von Allmen D. , Cohn S. L. , Matthay K. K. 
Published: March 2020

9505 Background: Myeloablative consolidation improves outcome for HR-NB pts, especially for pts in CR prior to consolidation. We assessed the toxicity and CR+VGPR rate of a dose-intensive multi-agent chemotherapy induction based upon the N7 regimen (JCO 22:4888, 2004) prior to myeloablative consolidation and peripheral blood autologous stem cell transplant (ASCT). Methods: Between 2/2001 and 3/2006, 489 eligible newly diagnosed HR- NB pts received the following induction consisting of 6 cycles of chemotherapy q 21 days. Cycles 1, 2, 4 & 6: cyclophosphamide 4.2 g/m2, doxorubicin 75 mg/m2, and vincristine 2 mg/m2 and Cycles 3 &5: cisplatin 200 mg/m2 and etoposide 600 mg/m2. Surgical resection of primary occurred after cycle 5. Following induction pts received purged or unpurged ASCT (as randomized), radiation, and then 13-cis-retinoic acid (13-cis-RA). Response was assessed after cycles 2 & 6 using the International Neuroblastoma Response Criteria and analyzed as intent-to-treat. Results: Median age was 3.1 yrs, 44% of 392 tumors tested had MYCN amplification. Fourteen pts (3%) died during induction (5 infection, 4 bleed into tumor, 4 compromised organ function from tumor, 1 unrelated to tumor/therapy). Patients experienced the following grade 3 & 4 toxicities at least once during induction: neutropenia 70%, thrombocytopenia 71%, hearing loss 6%, cardiac function 2% and renal function 3%. Documented infection occurred in 24% of cycles (90% bacterial, 3% viral, 7% fungal). Responses among the 489 pts at end of induction were CR 24%, VGPR 28%, PR 26%, SD 7%, and PD15%, with morphologically detectable bone marrow (BM) disease cleared in 87% and no disease remaining by MIBG scan in 55% of pts MIBG positive at baseline. Conclusions: Despite increased dose intensity of this regimen, toxicity was not excessive compared to prior HR-NB regimens. In a multi-center setting, the A3973 induction chemotherapy achieved morphologic BM clearance in 87% of pts prior to consolidation. The CR/VGPR rate of 52% is similar to that of prior less intensive regimens. The impact of this induction response on survival within the context of ASCT and 13-cis-RA on COG A3973 will be determined with longer follow-up. No significant financial relationships to disclose.
Molecular risk stratification in pediatric medulloblastoma
Authors: Pfister S. M. , Mendrzyk F. , Korshunov A. , Wittmann A. , Toedt G. , Benner A. , Werft W. , Kulozik A. , Scheurlen W. , Radlwimmer B. , Lichter P. 
Published: March 2020

9506 Background: Medulloblastoma is the most common malignant brain tumor and a significant cause of cancer mortality in children. Despite considerable therapeutic advances, prognosis remains poor, with a five-year-survival rate of about 60% emphasizing the urgent need for markers to allow for a more accurate tailoring of treatment intensity. Methods: We performed genome-wide analysis of DNA-copy number in 112 medulloblastomas using array-CGH. All patients had received craniospinal irradiation after surgery. Standard adjuvant chemotherapy with lomustine, cisplatin and vincristine or a regimen with equal potency had been administered to 73 patients. To identify novel prognostic markers, DNA copy number information was correlated with survival data using log rank and chi-square tests. For selected candidate genes identified by array-CGH, mRNA and protein expression were analyzed by real-time quantitative PCR, and immunohistochemically on tissue microarrays consisting of medulloblastomas from 189 patients. Results: Copy-number gains of chromosomes 6 and 17q, high-level amplifications of MYC and MYCN, and loss of 9p21.3 (CDKN2A locus) were identified as significant adverse prognostic markers; monosomy 6 was associated with good prognosis. Monosomy 6 and gain of 17q were mutually exclusive, whereas trisomy 6 almost always occurred in conjunction with 17q gain. Tumors with trisomy 6 and 17q gains exhibit strong up-regulation of MAP3K7 (chr. 6) and NLK (17q) mRNA, two key-enzymes of the non-canonical calcium-dependent Wnt-signaling pathway. Furthermore, this subgroup exclusively shows high mRNA-expression of several cancer-retina antigens (e.g. GNGT1, GNGT2, PDE6, RCV1, RDS and NRL). Tumors with monosomy 6, in contrast, display highly activated canonical Wnt signaling as indicated by nuclear protein expression of beta-catenin. Conclusions: We propose a model for the molecular risk stratification of medulloblastoma comprising five risk groups with significantly different survival using copy-number status of MYC, MYCN, and chromosomes 6 and 17q. Furthermore, we give evidence for a role of noncanonical calcium-dependent Wnt-signalling in medulloblastoma metastasis in a subset of tumors. Cancer-retina antigens could be used to facilitate the diagnosis and follow-up of this molecular subgroup. No significant financial relationships to disclose.
Successful treatment of childhood astrocytomas with cisplatin and irinotecan
Authors: Mora J. , Cruz O. , Parareda A. , de Torres C. , Guillen A. , Navarro R. , Garcia G. , Costa J. 
Published: March 2020

9508 Background: Childhood astrocytomas are a heterogeneous group of neoplasms for which non-surgical management is controversial. After a pilot study suggesting that irinotecan/cisplatin (I/C) may be effective for spinal cord astrocytomas in children (Mora et al, Neuro-Oncol 2007), we initiated a phase II trial for progressing astrocytomas with the aim of avoiding radiation therapy for low grade's and improve outcome for high grade's. Methods: The indication for adjuvant therapy was based upon histology, the extent of surgical resection, and the presence of clinical or neuroradiological signs of progression. Weekly Irinotecan (50 mg/m2 and 65 mg/m2 the last 2 cycles) and Cisplatin (30 mg/m2) for four consecutive weeks (1 cycle), and a total of 4 cycles was used. Results: Since 2004, 17 children aged 7m-17y were treated including 5 WHO grade I, 6 grade II, 3 grade III, and 3 non biopsied tumors: 2 intrinsic brain-stem tumors (BST) and 1 optic-pathway (OP) tumor. No patient had clinical signs of neurofibromatosis. Primary sites included 4 supratentorial, 3 BST, 3 OP, 1 cerebellar, and 6 spinal tumors. Gross total resection was performed in 1 case, subtotal in 4 and only biopsy in 9. Six patients received chemotherapy and one radiotherapy prior to the I/C regimen. Vomiting was easily controlled except for patients with BST. All but 2 patients, because of C allergy, completed the protocol with no documented ototoxic, renal, or GI side effects. Eleven (65%) pts had a complete clinical response, including 1 BST and all the spinal cord cases. Remarkably all the clinical responses were rapid, within the first 1–2 weeks of treatment. Twelve (70%) pts had a <25 [O1] % reduction of the tumor size at the end of therapy including 2 spinal cord cases that achieved complete radiological responses 10 months after the end of therapy. One BST patient progressed on therapy. Thus far, none of the low grade cases have received radiotherapy, although median f/u is only 1 year. All pts are alive and well. Conclusions: Remarkable clinicoradiological responses and avoidance of radiotherapy was obtained using the I/C regimen for childhood astrocytoma. No significant financial relationships to disclose.
Augmented Berlin-Frankfurt-Muenster (ABFM) regimen for children with standard-risk acute lymphoblastic leukemia (SR-ALL) and slow early response (SER)
Authors: Matloub Y. H. , Angiolillo A. , Bostrom B. , Stork L. , Hunger S. P. , Nachman J. , Sather H. , La M. , Carroll W. L. , Gaynon P. S. 
Published: March 2020

9511 Background: Numerous studies have shown that SER in ALL has a negative impact on outcome. Children's Cancer Group CCG-1882 demonstrated that post-induction intensification greatly improved the outcome of children with high-risk ALL and SER. Five year event-free-survival (EFS), and overall survival (OS) for the augmented regimen was 75 ± 4% vs 55 ± 4.5%, and 78 ± 4% vs 67 ± 5% for the standard regimen, p <0.001 and 02 respectively (N Engl J Med 1998; 338:1663–71). Methods: Therefore, COG-1952 and COG- 1991, studies for patients with SR-ALL, assigned the slow early responders to augmented therapy, while others were randomized according to the study design. Study eligibility criteria were similar for both, and included newly diagnosed children with National Cancer Institute SR criteria. COG-1952 accrued a total of 2,027 patients and COG-1991 accrued 3,054. In COG-1952 patients were deemed SER if their day-7 marrow had >5% blasts, and their day-14 marrow >25%. COG-1991 used the same criteria for SER, but also added patients whose day-7 marrow had >25% blasts and their day-14 marrow had >5% blasts to the SER group. This was based on the unfavorable outcome of this subgroup in COG-1952. The augmented therapy in COG-1991 like the CCG-1882 and COG-1952, was based on a COG-modified ABFM, but differed in using dexamethasone as the sole steroid and pegylated asparaginase as the asparaginase preparation, as compared to prednisone in induction and maintenance, and native E coli asparaginase. Results: Comparative groups with days 7 and 14 M3 marrows and unfavorable cytogenetics included 126 patients from COG-1991 and 81 from the COG-1952 were assigned to their corresponding ABFM regimens. Four year EFS and OS were 85% ± 5% and 90 ± 4% for CCG-1991 vs 61 ± 5.6% and 75 ± 5% for CCG-1952, p = 0.003 and 0.04 respectively. Conclusion: We conclude that the use of dexamethasone, and pegylated asparaginase greatly improves the outcome of children with NCI-SR with SER treated on a modified augmented BFM therapy, thus supporting the use of these agents in ALL therapy. No significant financial relationships to disclose.