bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of neuropathy in patients (pts) with multiple myeloma (MM) treated with thalidomide (thal)—Patterns of occurrence and the role of electrophysiologic monitoring
Authors: Mileshkin L. R. , Stark R. , Day B. , Seymour J. F. , Zeldis J. B. , Prince H. M. 
Published: March 2020

7618 Background: Given new treatment options for pts with MM, physicians are faced with the dilemma of how best to sequence these drugs in order to optimize efficacy and toxicity. Peripheral neuropathy frequently limits the duration of treatment (Rx) with thal. In this study we assessed the utility of serial nerve electrophysiological studies (NES) to detect the onset of neuropathy, and assessed the time course of occurrence and possible clinical and Rx-related predictive factors. Methods: 75 pts with relapsed/refractory MM were enrolled in a multi-centre trial of thal. In addition to clinical assessment, pts underwent sensory and motor NES at baseline and every 3 months in order to identify neuropathy. We examined the value of baseline and serial NES for development of neuropathy, with time to development of neuropathy according to clinical or NES criteria compared using Kaplan-Meier analysis. Differences between pt and Rx-related variables were compared using a Mann-Whitney U-test or a Fisher’s exact test. Results: Thirty nine percent had some NES abnormalities at baseline. Pts were treated with thal at a median dose intensity of 373 mg/day and followed for a median of 18 months (range 6–26). Thirty-one of the 75 pts (41%) developed neuropathy during thal Rx, with 11 (15%) ceasing thal due to neuropathy. The actuarial incidence of any neuropathy increased from 38% at 6 months to 73% at 12 months with 81% of responding pts developing this complication. The use of NES did not reliably predict the imminent development of clinical neuropathy requiring cessation of thal. Nor were pt age, gender or type of prior therapy (ie vincristine) predictive. Development of neuropathy was related to duration of thal exposure with a median time of 268 days thal in those who developed neuropathy compared to 89 days in those who did not (p = 0.0001). Cumulative dose or dose intensity received were not predictive. Conclusions: The majority of pts will develop peripheral neuropathy given sufficient length of thal Rx and to minimize the risk of neurotoxicity, therapy should be limited to less than six months. NES monitoring provides no clear benefit over careful clinical evaluation for the development of clinically significant neuropathy. [Table: see text]
Correlation of bone marrow angiogenesis and response to thalidomide dexamethasone in multiple myeloma
Authors: Kumar S. , Greipp P. R. , Haug J. L. , Gertz M. A. , Blood E. , Rajkumar S. V. 
Published: March 2020

7621 Background: Thalidomide (Thal) in combination with dexamethasone (Dex) is an effective therapy for myeloma (MM). Though initially evaluated in MM because of its anti-angiogenic properties, it is not clear how much this contribute to its anti-MM effects. We examined whether the degree of angiogenesis influences response to Thal + Dex, as well as effect of therapy on marrow angiogenesis. We also examined whether expression of angiogenic cytokines by MM cells affect response to therapy. Methods: A total of 207 pts with newly diagnosed MM were randomized on the ECOG phase III trial (E1A00) to either Thal-Dex or Dex alone. Bone marrow microvessel density (MVD) was determined on 88 pts at diagnosis and at 4 mos after therapy in 25 pts. Expression of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) by MM cells was determined by RTPCR on 60 pts at diagnosis and on 22 pts at 4 mos. In addition, the percentage of marrow PCs in apoptosis was determined at diagnosis and 4 mos in 43 pts. A decrease in the serum M protein by 50% or in its absence, a decrease in urine M protein by 50% was considered a response. Results: The median BM MVD at diagnosis was 33 (3–118), and was similar in the pts responding to therapy (36.4) and in the non responders (45.4). We also separately looked at those receiving the combination vs. Dex alone, and did not find any correlation. The expression of FGF and VEGF in the PCs did not predict response to therapy with either the combination or Dex. Among the 17 responding pts, MVD decreased by a mean of 12 compared to an increase in the mean MVD of 3 among the non responders (P = NS). There was no significant correlation between the level of FGF or VEGF expression and the marrow MVD. There was no correlation between the percentage of myeloma cells in apoptosis at baseline and response to therapy. Conclusion: While the anti-angiogenic activity of Thal may play a role in its anti-myeloma effect, baseline MVD or tumor cell expression of angiogenic cytokines do not predict resistance or response to Thal-Dex or Dex alone. The findings here confirm previous observations that marrow angiogenesis is not related to the degree of secretion of angiogenic cytokines by individual cells, but rather the cumulative effect of the tumor mass. No significant financial relationships to disclose.
Visual complications in childhood cancer survivors: A Childhood Cancer Survivor Study report
Authors: Whelan K. , Mertens A. , Castleberry R. , Mitby P. , Kawashima T. , Sklar C. , Packer R. , Waterbor J. , Blatt J. , Robison L. 
Published: March 2020

9006 Background: The Childhood Cancer Survivor Study (CCSS) is an NIH funded project (U01-CA 55727) designed to study the effects of childhood cancer treatment on long- term survivors. Previous studies have found associations between certain cancer therapies and visual complications. Methods: The CCSS is a retrospective cohort study investigating health outcomes of long-term survivors (> 5 years) diagnosed and treated between 1970 and 1986 compared to a randomly selected sibling cohort. Questionnaires were completed by 14,362 survivors of childhood cancer and 3,901 sibling controls. Analysis determined the first occurrence of 8 visual conditions in 3 time periods: during therapy, end of therapy to 5 years post diagnosis, and greater than or equal to 5 years post diagnosis. Multivariate analyses, adjusting for current age and gender, determined the relative risks (RR) and 95% confidence interval (CI) of visual conditions by treatment exposure. Results: Survivors had statistically significant increases in the RR of cataracts, glaucoma, legal blindness, double vision, retinal condition, and dry eyes, across all time periods, when compared to siblings. During the time period of 5 or more years post-diagnosis, statistically significant positive associations were present for cataracts and other head radiation, craniospinal radiation, total body radiation, and prednisone; glaucoma and craniospinal radiation; double vision and craniospinal radiation; legally blind and other head radiation and craniospinal radiation; and dry eyes and other head radiation, total body radiation, and dexamethasone. There were no statistically significant associations between treatment factors and retinal conditions. Conclusions: Childhood cancer survivors are at risk of developing visual complications and treatment related factors are important determinants of this risk. Follow-up is needed to evaluate the impact of visual conditions on quality of life. [Table: see text] No significant financial relationships to disclose.
Prognostic significance of myeloid associated antigen expression in childhood acute lymphoblastic leukemia in Peru
Authors: García J. L. , Wachtel A. E. , Pérez C. , Marcial J. , Dyer R. , Doimi F. 
Published: March 2020

9030 Background: The prognostic significance of coexpression of myeloid antigens in pediatric patients with acute lymphoblastic leukemia (ALL) has been reported by several authors, with a frequency that has ranged widely. All of these authors are from developed countries, the aim of this study is to evaluate the prognostic significance of these antigens in childhood ALL in a developing country. Methods: We retrospectively reviewed 729 newly diagnosed patients with ALL under 14 years of age, who had a bone marrow flow cytometry performed at our institution, between 1996–2002. Clinical data and treatment outcomes were reviewed and compared between patients with ALL who expressed myeloid antigens and those who did not using chi-square test. Results: 729 medical charts were studied, 81.6% of them were B-common, 8.2% were pro-B, 8.2% were T-cell and 2.1% were pre-B ALL patients. Overall frequency of myeloid antigen expression was 36.6%. The most frequent specific antigens found were: CD13, 15.5%; CD15, 6.0% and CD33, 4.5%. Evaluating the B-common ALL patients the presence of myeloid antigens rises to 43%. Patients who had coexpression of myeloid antigens had a relapse rate (any site) of 49.2% while 36.3% who had no coexpression had a relapse (p=0.001). There has also been statistical significance in bone marrow response on day 14 of induction with 64.9% having less than 5% blasts in the group without coexpression and 46.4% in the group with coexpression (p<0.0001). Conclusions: The present retrospective review shows the presence of associated myeloid antigens in our ALL patients in 36.6%. We have shown that it is an adverse prognostic factor for childhood ALL in a developing country, unlike reports from other centers in developed countries. No significant financial relationships to disclose.
RISK-adapted treatment of Burkitt’s lymphomas in childern
Authors: Mohran T. Z. , Ebeed E. N. 
Published: March 2020

9034 Background and Purpose: Various treatment regimens have been implemented in an attempt to improveDFS of children with B cell lymphoma. We evaluates the treatment results of children with stage I, II III Burkitt’s lymphoma at 2 centers in Egypt. Patients and Methods: Patient recruitment in this open non-randomized study occurred from July 1998 to Dec 2002 . 97 patients with pathologically proven Burkitt’s lymphoma stage I to III were diagnosed . All patients were subjected to history, clinical examination, CSF, bone marrow and radiological evaluation. Patients with stage IV were excluded from. Patients with stage I and II received 4 cycles of (A→B→A→B), while patients with stage III received 8 cycles of (A→B→A→B→A→B→A→B). Intrathecals were given during the first 4 cycles. Cycle A was formed of cyclophosphamide, adriamycin, vincristine, cytosine arabinoside, plus intrathecal MTX and cytosine arabinoside. Cycle B was formed of ifosfamide, vepeside, methotrexate, vincristine and intrathecal cytosine arabinoside and mtx. Results: Patients was 97, their age ranged between 2 and 18, theirmean age was 8.6 and median was 8 years.The male to female ratio was 3.8:1. The primary site was the abdomen in 49 patients (50%), peripheral lymph node enlargement was encountered in 38 patients (39.1%). Jaw involvement occurred in 7 patients (7.2%). Two patients (2%) presented with Tonsilar mass and only one patient presented with mass at inner canthus (1%). Patients were staged according to St. Jude staging system. Patient distribution was as follows: Stage I, 18 (18.6%); stage II, 31 (32%); stage III, 48 (49.5%). In August 2003, 90 patients were in continuous complete remission with a follow up period ranged between 8 months and 53 months and a median 39 months. The projected 3 years DFS for the whole group was 93.8%±2.5%. Correlation between DFS and LDH was significant (P=0.01) while correlation with age, sex and stage was insignificant. Conclusions: Treatment result with the prescribed protocol is extremely good. The outcome of non advanced Burkitt’s lymphoma in rural areas of Egypt is comparable to all studies in developed countries. High dose methotrexate is not a must to improve survival of stage I-III Burkitt’s lymphoma. Initial serum LDH level is an important prognostic factor. Key words: Childhood, Burkitt’s lymph. No significant financial relationships to disclose.
Radiotherapy plus concomitant and adjuvant temozolamide for newly diagnosed pediatric high-grade astrocytoma
Authors: Abdel Wahab M. M. , El-Hosseini H. , Eezz El-Arab L. R. 
Published: March 2020

9042 Background: to evaluate the potential survival advantage of adding temozolamide (TMZ) concomitantly and adjuvant to radiotherapy (RT) as regard time to progression (TTP) and overall survival in addition to its safety and tolerability in pediatric high grade astrocytomas. Methods: A total of 29 pediatric patients newly diagnosed, histologically proven glioblastoma multiforme (GBM) or anaplastic astreocytoma (AA) were randomized, to radiotherapy alone (14 patients) or radiotherapy and concomitant (TMZ) 150mg/m2/d for 5 days every 28 days followed by up to 6 cycels of adjuvant TMZ (15 patients). Results: The median time to progression was significantly prolonged in patients treated with RT/TMZ compared to those treated with RT alone (14 months Vs 7 months respectively) (P<0.05). The median overall survival in the combined treatment Vs monotherapy was 23 months and 13 months respectively (P<0.01). Non hematologic adverse events were similar between both groups while grade 3 & 4 hematologic toxicities occurred in 20% only of the RT/TMZ arm (2 patients experienced grade 3 thrombocytopenia and 1 patient developed grade 4 neutropenia). Conclusions: This study demonstrate a significant survival benefit for the addition of TMZ to treatment of pediatric patients with high grade astrocytpoma and it’s safety, well tolerability which allows it to be given concurrently with RT, followed by additional adjuvant cycles. No significant financial relationships to disclose.
Palliative radiotherapy in pediatric malignancies
Authors: Bhasker S. , Turaka A. , Mohanti B. K. , Bajpai V. 
Published: March 2020

9050 Background: To evaluate the role of palliative radiotherapy in the management of incurable pediatric malignancies. Methods: Records of 40 pediatric patients treated between Jan’ 2003 and Nov’ 2005 were reviewed and analyzed retrospectively. All of theses 40 children received palliative external beam radiotherapy for symptom control. Palliative radiotherapy was given either as single modality or in addition to surgery, chemotherapy and symptom relief drugs. Information recorded for each patient included age, sex, and extent of disease, histological types, symptomatology, treatment methods and symptom relief. Results: There were 28 boys and 12 girls in the age group of 1 to 18 years, with a median age of 14 years (range of 1–18 years). Predominant symptoms were swelling with or without pain, bleeding, and weakness of limbs. The median duration of symptoms was 90 days (range of 4–50 days). The diagnosis of these children varied with different histologies, most in the group of malignant round cell tumors (11), retinoblastoma (4), neuroblastoma (4), AML with chloromas (3), Ewing’s sarcoma (4). All patients presented with advanced stages of disease. Out of 40 patients 18 (45%) had disseminated disease at presentation. Nine patients underwent surgery while 32 patients received chemotherapy and all but two patients received symptom relief drugs in addition to palliative radiotherapy. The various dose schedules were either 5 Gy or 8 Gy for single fraction treatment while the dose schedules for fractionated radiotherapy ranged from 20 Gy in 5 fractions to 30 Gy in 10 fractions. Four patients showed complete resolution, 20 patients showed good, while 15 patients had little, 1did not have any relief in their symptoms. At the completion of multimodality treatment, 18 patients had partial response, 8 patients had progressive disease, 8 had stable disease and two patients had complete response. The disease status of 4 patients could not be known. Conclusions: The role of radiotherapy as palliative modality in children with locally advanced lesions provides better symptom relief in combination with other modalities of treatment. No significant financial relationships to disclose.
Feasibility and acute toxicities of outpatient ifosfamide infusions in children and adolescents with cancer
Authors: Macedo C. R. , Nogueira P. K. , Ginani V. C. , Gouveia R. V. , Petrilli A. S. 
Published: March 2020

9055 Background: Ifosfamide (IFO) is very effective and widely used in pediatric oncology protocols. Patients are usually admitted to receive IFO infusions due to potential urological and neurological complications. The current study was conducted to assess the feasibility of outpatient IFO infusions in children and adolescents with cancer, the compliance of the patients and their parents, and the acute toxicities in this setting. Methods: All patients with newly diagnosed solid tumors included in protocols with at least three cycles of IFO/mesna were eligible for this study. IFO was administered I.V. over one hour. Doses varied according to the underlying malignancy and protocol from 2.5–3.0g/m2/day × 3 days to 2.7g/m2/day × 5 days. Three doses of mesna were administered intravenously in the outpatient clinic at 75% of the IFO dose divided on hours 0, 3 and 6 and a fourth dose of mesna was given as oral tablets at home 12 hours after IFO. Hydration was 2L/m2 I.V. over 5 hours in the hospital, followed by another 1L/m2 P.O. at home. Kidney function was assessed before, during, and after treatment through glomerular filtration rate; sodium, magnesium, calcium, uric acid renal excretions; urinary phosphate threshold and retinol-binding protein. Results: From November 2003 to August 2005, 30 patients received a total of 160 IFO cycles. Compliance was 100%. The incidence of grades 3 and 4 toxicities in all IFO cycles was: gastrointestinal 15%, leucopenia 92%, neutropenia 88%, thrombocytopenia 29%, hepatotoxicity 3%, and genitourinary 7%. No patient had gross hematuria, neurotoxicity or had to be admitted for chemotherapy. One third of the patients developed subclinical tubular nephropathy. Conclusions: Ambulatory infusion of IFO is safe and toxicities are comparable to the expected with inpatient administration. No significant financial relationships to disclose.
Clinical utility of FDG-PET for evaluation of the viability in post-chemotherapeutic residual lesions in pediatric solid tumors
Authors: Hosono A. , Makimoto A. , Tsuji N. , Kawamoto H. , Watanabe A. , Tateishi U. , Terauchi T. 
Published: March 2020

9067 Background: Exact evaluation of viability in post-chemotherapeutic residual lesions in patients with solid tumors should allow us to select the appropriate therapeutic options. F-18 fluorodeoxyglucose position emission tomography (FDG-PET) is one of the promising modality to evaluate it without invasive procedure. Methods: The cohort is a total of 14 patients with pediatric solid tumors (rhabdomyosarcoma 7, Ewing sarcoma 4, Wilms tumor 2 and neuroblastoma 1), which are either newly diagnosed or newly relapsed between January 2005 and December 2005. A total of 15 residual tumors from the 14 patients after chemotherapy underwent 51 FDG-PET scans. Seven residual tumors out of 6 patients, who were newly diagnosed, and another 8 tumors out of 8 patients, who were relapsed, were evaluated after induction or reinduction chemotherapy. Parameters of FDG-PET were assessed by area of FDG uptake and standardized uptake values (SUV). Results of FDG-PET were compared either with histological examination of the residual tumors (n=11) or with the clinical status 6-month after the last FDG-PET (n=4) in order to judge whether the findings of FDG-PET were true or false. Results: Three of 15 residual lesions showed increased SUV, while 12 lesions obtained negative SUV. Three lesions with positive SUV consisted of 2 true-positive and 1 false-positive lesions. Among twelve lesions were negative SUV, 11 lesions were true-negative, and 1 was false-negative. The sensitivity and specificity of FDG-PET in predicting the viability of residual lesions were 66% and 91%, respectively. A lesion of rhabdomyosarcoma which obtained negative SUV in FDG-PET histological showed viable cells. A lesion of another rhabdomyosarcoma which showed positive SUV was evaluated as inflammatory lesion. Conclusions: Although FDG-PET showed excellent sensitivity and fair specificity in predicting the viability of residual lesions in patients with pediatric solid tumors, possibility of false-negativity should give us a caution not to rely on FDG-PET to judge the termination of therapy. No significant financial relationships to disclose.
A multicenter phase 2 consortium (P2C) study of the mTOR inhibitor CCI-779 in advanced soft tissue sarcomas (STS)
Authors: Okuno S. H. , Mahoney M. R. , Bailey H. H. , Adkins D. R. , Maples W. J. , Ettinger D. , Fitch T. R. , Bot B. M. , Erlichman C. E. 
Published: March 2020

9504 Background: CCI-779 inhibits the mammalian target of rapamycin (mTOR), a Ser/Thr kinase involved with the initiation of mRNA translation, showing growth inhibition in many tumor cell types. The primary goal was to evaluate the confirmed response rate (RR) of CCI-779 in advanced STS. Methods: Eligibility included pts ≥ 18 yrs, measurable advanced STS, PS 0–2, adequate laboratory function (including Chol ≤ 350 mg/dL and TG ≤ 400 mg/dL), no prior chemo for advanced disease (adjuvant chemo allowed), and no brain metastases. Following premedication with an antihistamine, CCI-779 was given intravenously at 25 mg over 30 minutes on days 1, 8, 15, and 22, repeated q 4 wks. A total 50 pts were to be enrolled, if there were 2 responses at the time of an interim analysis conducted on the initial 20 patients. Pre- and post-treatment blood was collected to evaluate p70S6 kinase, S6 phosphorylation, inhibition of mTOR, and sirolimus levels. Pre-treatment paraffin-embedded tumor tissue was used to evaluate immunohistochemistry markers (including, EFGR, c-Myc, Her2, 4EBP1). Results: 41 eligible pts (18 male, median age 62 yrs with range 28–79) were enrolled from 11/04 to 9/05. 71% presented with high grade tumors. Histologic subtypes include: malignant fibrous histiocytoma (MFH) (7), sarcoma NOS (9), fibrosarcoma NOS (3), liposarcoma NOS (5), leiomyosarcoma (8), endometrial stromal (1), synovial (1), hemangio/angiosarcoma (2), hemangiopericytoma NOS (1), and neurofibrosarcoma (1). 42% (16/38) evaluable pts had Gr 3+ events at least possibly related to CCI-779, 1 of which was Gr 4 hyperglycemia (see table). One pt having extremity fibrosarcoma, achieved a PR after 2 cycles lasting at least 36 weeks. Twenty-eight pts have progressed and 10 have died. Estimated median time to progression is 2 months (95% CI 1.8–3.5). Conclusions: Despite an acceptable toxicity profile, CCI-779 failed to demonstrate promising activity in pts with advanced STS. Results of the correlative studies are pending. Supported by N01 CM17104. [Table: see text] No significant financial relationships to disclose.