bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiographic tumor response in pediatric patients with newly diagnosed localized (LOC) or metastatic (MET) Ewing’s sarcoma (EWS) following neoadjuvant chemotherapy
Authors: Chuk M. K. , Balis F. M. , Mackall C. , Hawkins D. , Avila N. , Widemann B. C. , Helman L. J. , Fox E. 
Published: March 2020

20008 Background: Standard treatment for EWS includes vincristine, doxorubicin, cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE). Using this therapy, overall survival is 70% in patients with LOC EWS and 30% in patients with MET EWS. We compared the radiographic response to VDC and IE in patients with LOC or MET EWS. Methods: We conducted a randomized trial comparing pegfilgrastim to filgrastim in patients treated with VDC (cycles 1, 2, 5, 9, 11, 13) and IE (cycles 3, 4, 6–8, 10, 12, 14). Local control with radiation or surgery was initiated after cycle 5. We assessed radiographic response after VDC (C1,2) and IE (C3,4) using 1-dimensional (RECIST) and 2-dimensional (WHO) criteria. Measurements were performed using MEDx. Results: Twenty-one patients with EWS, median age 20y (6–25y), were enrolled; 16 were evaluable for this analysis. Primary tumors were in extremity (n=5) or central axis (n=11). Eight patients had MET disease (pulmonary only, n=4). Median (range) decrease in tumor size by WHO after C4 was 61% (40–92%) for LOC and 83% (47–94%) for MET. Decrease by treatment is presented in the table . Overall responses after 4 cycles for LOC patients were 5 PR, 3 SD using RECIST, and 6 PR, 2 SD using WHO. For MET patients, overall responses were the same using RECIST and WHO, 7 PR, and 1SD. Conclusion: Patients with MET EWS responded as well as those with LOC EWS after 4 cycles of neoadjuvant chemotherapy. Similar overall response was demonstrated using RECIST or WHO. Tumor response after VDC was greater than after IE, possibly due to sequence of administration, but patients had continued tumor response with IE. [Table: see text] No significant financial relationships to disclose.
A phase II trial of AZD2171 (cediranib), an oral pan-VEGF receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma
Authors: Batchelor T. , Sorensen A. G. , Ancukiewicz M. , Duda D. G. , Louis D. N. , Plotkin S. R. , Ivy P. , Wen P. Y. , Loeffler J. S. , Jain R. 
Published: March 2020

2001 Background: AZD2171 (cediranib) is a potent, oral pan-VEGF receptor tyrosine kinase inhibitor with a half-life of 20 hours compatible with once-daily dosing. A primary target of AZD2171, VEGFR2, is expressed on glioblastoma endothelium. We have demonstrated normalization of tumor vessels in recurrent glioblastoma patients treated with daily doses of AZD2171. Normalization has rapid onset, is reversible and is associated with alleviation of brain edema [Cancer Cell 2007; 11: 83]. Methods: In this phase II study of 30 recurrent glioblastoma subjects the primary endpoint was the proportion of patients alive and progression-free at 6 months (APF6). Secondary endpoints include radiographic response proportion; progression-free survival; overall survival and toxicity. At this time we are presenting radiographic response data and toxicity on the first 16 consecutive patients and APF6, PFS and OS on all 30 patients. Complete information will be available on all 30 patients at the time of presentation. Results: Twenty-eight patients have experienced disease progression and two patients remain in follow-up without progression. The primary and secondary endpoints are tabulated below: Only one of the first 16 patients was removed from the study due to toxicity (fatigue). Dose limiting toxicities of hypertension, fatigue and diarrhea were observed in 9/16 patients. There were no intracerebral hemorrhages. AZD2171 alleviated brain edema, a major cause of morbidity in glioblastoma patients, and had a steroid-sparing effect in the first 16 patients enrolled. Blood biomarkers were serially assessed and elevated levels of bFGF, SDF1a and viable circulating endothelial cells correlated with disease progression. Conclusions: AZD2171 has activity in patients with recurrent glioblastoma. Combination studies of AZD2171 with radiation and chemotherapy are planned. [Table: see text] [Table: see text]
Valproic acid enhances etoposide induced cytotoxicity in neuroblastoma cells
Authors: Aguilera D. G. , Das C. , Wolff J. , Zage P. , Gopalakrishnan V. 
Published: March 2020

20010 Background: Metastastic neuroblastoma is resistant to treatment and prolonged response is difficult to achieve therefore new therapies are necessary. Etoposide, a topoisomerase II inhibitor is often used for its treatment. Valproic acid (VPA) has histone deacetylase inhibitor (HDI) activity. Epigenetic alterations described in neuroblastoma tumors make VPA a good candidate to evaluate for potentiation of etoposide-mediated cytotoxicity. We evaluate the effects of VPA in combination with etoposide in neuroblastoma cells. Methods: Human neuroblastoma cell lines SKNAS and SKNSH were incubated with 1.5 mM VPA and increasing concentrations of etoposide from 1x10-6 to 1 mM. Cell viability assay were measured with MTT assays. Results: We observed that VPA and etoposide independently decreased cell viability in a time and concentration dependent manner. The co-incubation with both drugs greatly enhanced the cytotoxicity of etoposide. IC50 for SKNSH cells treated with etoposide were approximately 1x10–3, 1.8x10–4, and 3x10- 5mM at 24, 72 and 96 hours, respectively. With the addition of VPA we found that cell viability was reduced approximately by 10 fold at each time point. At 72 and 96 hours 100 percent cell death was achieved at 0.1 mM of etoposide. IC50 for SKNAS cells treated with etoposide were approximately 1.8x10–3 mM and 6x10–4 mM at 72 and 96 hours, respectively. With the addition of VPA, IC50s were reduced by approximately 5 fold at the same exposure times. Further confirmation of synergistic activity was demonstrated with the use of the fraction product method of Webb formula. Conclusions: Our results demonstrate that VPA potentiates the cytotoxic effects of etoposide on neuroblastoma cells. by altering gene expression and rendering the cells more sensitive to etoposide induced cell death. Finally, since these agents have a proven track record of safety and efficacy in patients with neuroblastoma, this data supports the use of this combination in a phase I trial in patients with neuroblastoma. No significant financial relationships to disclose.
Result of childhood acute lymphoblastic leukemia protocol (INCTR) from a developing country
Authors: Mukhopadhyay D. , Gupta P. , Mukhopadhyay S. , Chitalkar P. , Banavali S. D. , Advani S. H. , Adde M. , Magrath I. 
Published: March 2020

20015 Background: Acute Lymphatic Leukemia in children is a curable disease in the range of 80–90 % in developed Countries by aggressive protocol like BFM, St. Judes’. In developing Countries like ours, patients can’t tolerate those aggressive protocol because of Socio- economic and nutritional factors. The less aggressive Protocol like INCTR (International Network for Cancer Treatment & Research) are suitable in developing Countries like ours. The aim of our study was to see outcome of childhood ALL patient with INCTR protocol and tolerability of the protocol in Indian-asian population. Methods: We treated 480 Children (age range 1–25 years, median age of 11 yrs) with INCTR Protocol at Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata, India, a tertiary cancer centre from Eastern India during period from April ’99 to Dec ’06. There was female preponderance in the study. Fever 283 (58.9%), lymphadenopathy 211 (43.9%) and haepatosplenomegaly 153 (31.8%) were the major clinical presentation. Forty-three (8.9%) patients were present with hyper Leukocytosis. C-ALL phenotype were the largest group though the incidence of the T-ALL were quite high (27.9%). Results: Remission induction were seen in 446 (92.9%) of the patient. In a follow-up period of 88 months (with an average of 54 months) the disease-free survival ( DFS) was 66.8% (321 patients) with an overall survival of 73.9% (355 patients). The isolated bone marrow relapse was seen in majority of the cases 40 (8.33%) and the major relapse was in maintenance and first 6 months of completion of therapy. The major cause of morbidity was infection 316 (65.8%) followed metabolic complications 81 (16.8%), hemorrhage 52 (10.8%), neurologic 10 (2.08%), hepatitis 6 (1.25%) and pancreatitis 5 (1.04%). The major cause of the mortality was infection 75%(360 patients) followed progressive disease 7.91% (38 patients) and Hemorrhage 5.83%( 28 patients). Conclusions: The data of acute lymphatic leukemia from a developing country is encouraging. The protocol was well tolerated by India- asian population. No significant financial relationships to disclose.
Radiation induced lung injury in survivors of childhood cancer
Authors: Stegner M. M. , Luckett P. M. , Fitzgerald J. E. , Eshelman D. , Cochran C. , Leavey P. J. 
Published: March 2020

20017 Background: The purpose of this study was to examine survivors of childhood cancer, treated with whole lung irradiation (WLI), for signs of pulmonary insufficiency and to correlate pulmonary function test (PFT) results to symptoms of pulmonary dysfunction as detected using the St. George’s Respiratory Questionnaire (SGRQ). Methods: A cross-sectional study was conducted on eligible patients (>2 years from WLI and <18 years at time of diagnosis) who are followed in our institution’s cancer survivor program. Participating patients had a history and physical examination and PFTs performed pre and post bronchodilator challenge. Patients (or their guardians) also completed the SGRQ. The SGRQ, validated for patients 17 to 80 years, generates four values that define respiratory dysfunction: a Symptoms score, an Activity Score, an Impact score, and a Total score. Results: Twenty eligible patients were identified, 12 of whom consented to participate in this study (11 Wilms, 1 Ewing sarcoma). The median current age was 18.4 years (7.5 to 43 years; n=6 < 14 yrs), while patients received WLI (1,200 cGy n=10, 1500 cGy n=2) at a median age of 4.4 years of age (1.7 to 8.7 years). The median time from radiation therapy was 12.6 years (4.7 to 34.3 years). All patients denied smoking, 4 had a history of asthma and all had a normal lung exam. Ten patients had PFTs, 5 of whom (4/5 adults and 1/5 children) had a restrictive pattern noted by PFTs. One further patient (7.5 yrs of age) had a total lung volume 70% predicted but a forced vital capacity 86% predicted. In the pediatric patients (<14 years currently) the FEF 25–75 (4/5) and SGaw (5/5) were increased following treatment with bronchodilator. Twelve participants completed the SGRQ, 4 had elevated total scores (22, 32, 37 and 64). 1 patient with echocardiographic evidence of a dilated cardiomyopathy had an elevated total score but normal symptom score. One patient with a recorded acute pneumonitis after WLI, now 18 years later had normal PFTs and normal SGRQ scores. No correlation was seen between PFT results and SGRQ scores. Conclusions: A restrictive lung function pattern is more common at a later age following WLI in childhood. Mid-expiratory flow and airway conductance following bronchodilator were increased in children. The functional significance of these findings requires further study. No significant financial relationships to disclose.
Results of cisplatin-based chemotherapy in inoperable hepatoblastoma during last two years at a single institute
Authors: Patel K. M. , Shah S. A. , Patel A. A. , Shah P. M. , Shukla S. N. , Parikh B. J. , Anand A. S. , Talati S. S. , Srivastav R. K. , Dave R. I. 
Published: March 2020

20027 Background: Total surgical excision and adjunctive chemotherapy are cornerstones of treatment of hepatoblastoma in children. But many are unsuitable for radical surgery at diagnosis due to extensive intrahepatic and/or extra hepatic disease. We assessed 18 consecutive cases during the last two years, all of whom presented with unresectable tumor, treated in our center with neoadjuvant chemotherapy,in order to analyze the clinical profile and response to treatment. Methods: A retrospective analysis of patients who presented to our institute during January 2004 to January 2006 was carried out. All patients were biopsy proven hepatoblastoma. One patient was operated without anterior chemotherapy outside our institute .Two patients had lung metastasis. Rest all had stage 3 disease. All the patients were given cisplatin [90 mg/m2] and continuous infusion doxorubicin [80 mg/m2 over 4 days]. The response to therapy was assessed. Results: Mean age of presentation was 3 years and 4 months [range 1 year to 11 year]. M:F ratio was 4:1. Most common presenting complaint was an asymptomatic abdominal mass felt by the parent. All the patients had tumour in right lobe. Mean alpha fetoprotein level was 0.14 million and the range was from normal to 1.24 million. None of the patients were positive for hepatits B or hepatitis C. After three cycles of chemotherapy, seven of the seventeen patients had adequate down staging of the disease so as to undergo successful resection. There was one post operative mortality. All of them completed total of six cycles of chemotherapy. Ten patients had unresectable tumour even after six cycles of chemotherapy. All of them had reduction in the size of primary tumor and decreased alpha fetoprotein level .There was no chemotherapy related grade 3 or grade 4 toxicity. Conclusions: Hepatoblastoma occurs at a later age in Indian patients as compared to that seen in western countries. Cisplatin and adriamycin are quite effective in downstaging hepatoblastoma. Since these agents are cheap and have minimal toxicity they should be used frequently. No significant financial relationships to disclose.
N047B: NCCTG phase II trial of vorinostat (suberoylanilide hydroxamic acid) in recurrent glioblastoma multiforme (GBM)
Authors: Galanis E. , Jaeckle K. A. , Maurer M. J. , Reid J. M. , Ames M. M. , Giannini C. , Hardwick J. S. , Moore D. F. , Zwiebel J. A. , Buckner J. C. 
Published: March 2020

2004 Background: Vorinostat is a histone deacetylase inhibitor that represents a rational therapeutic target in GBM. Methods: Recurrent GBM patients (pts) having received = 1 prior chemo regimen for progressive disease were eligible. Vorinostat dose was 200 mg bid x 14 days q 3 weeks. We applied a phase II design which had 90% power to declare the regimen active if the study PFS6 rate was 25%, a 15% rate increase over PFS6 in historical controls (10%). Results: 68 patients were treated. Grade 3+ non-hematologic toxicity consisting mainly of fatigue, diarrhea and dehydration occurred in 23% of pts; Grade 3+ hematologic toxicity consisting mainly of thrombocytopenia occurred in 25% of pts. Intra-patient dose escalation to 300 mg bid resulted in higher incidence of grade 3+ thrombocytopenia (45%) and was aborted. Pts receiving enzyme-inducing anticonvulsants (EIAC) had significantly less grade 3 + non-hematologic toxicity (p=0.01) and grade 3/4 thrombocytopenia (p=0.04). Pharmacokinetic analysis showed lower vorninostat C-max and AUC (0–24h) values and higher vorinostat-glucuronide C-max and AUC (0–24h) values in EIAC pts, although this did not reach statistical significance. The trial met the prospectively defined primary efficacy endpoint at the planned interim analysis with 5 of the first 22 patients (23%) being progression-free at 6 mo. RNA array analysis, performed in paired baseline and post-vorinostat treatment samples in a separate subgroup of 5 surgical recurrent GBM pts, who received vorinostat for 6 doses prior to surgery, showed upregulation of E-cadherin (p=0.02), thus indicating a biologic effect of the HDAC inhibitor on the glioblastoma tumors. Histone acetylation, Akt, phospho-Akt, P21Waf1/Cip1 and P27Kip1 expression analysis in all patients and correlation with outcome is ongoing. Conclusions: Vorinostat is well tolerated in recurrent GBM patients. EIAC patients have less toxicity, likely due to increased vorinostat metabolism via glucuronidation. Interim efficacy analysis is indicative of antitumor activity. Final efficacy analysis, RNA array data and correlative tissue analysis will be reported. No significant financial relationships to disclose.
Motexafin gadolinium (MGd) combined with whole brain radiation therapy prolongs time to neurologic progression in non- small cell lung cancer (NSCLC) patients with brain metastases: Pooled analysis of two randomized phase III trials
Authors: Shapiro W. R. , Mehta M. P. , Langer C. , Bezjak A. , Timmerman R. , Brachman D. , Suh J. , Smith J. A. , Phan S. , Renschler M. F. 
Published: March 2020

2010 Background: In 2 randomized trials, whole brain radiation therapy (RT) plus MGd prolonged time to neurologic progression (TNP) in NSCLC patients (pts) with brain metastases (BM). In this report, results of a pooled analysis from both trials are presented. Methods: In trial 9801, 401 pts with BM from solid tumors were randomized to RT (30 Gy) or RT+MGd, 5 mg/kg qd x 10 days. The subgroup of 251 pts with NSCLC is included in this analysis. In trial 0211, 554 pts with BM from NSCLC were randomized to the same treatments. In both trials, eligibility included a KPS = 70, no liver metastases, and = 1 site of extracranial metastasis. In both trials, a primary endpoint was time to neurologic progression determined by a blinded events review committee (ERC), incorporating data from neurologic exams, neurologic symptom collection, and neurocognitive tests. Results: 805 pts received RT (N=403) or RT+MGd (N=402). Most pts had multiple BM (80%), extracranial metastases (47%) and presented with neurologic deficits (84%). Treatment with MGd was well tolerated, with 93.3% of intended doses administered. Most common MGd-related grade 3+ adverse events were hypertension (4.6%), and fatigue (2.8%). TNP in the RT+MGd group was 15.4 mo, significantly longer than the 9.0 mo for the RT alone group, p=0.016, HR=0.74 (95% CI 0.57–0.95). The results of both studies are consistent, as shown in the table below. Similar results were observed in time to investigator-determined neurologic progression (p=0.015, HR=0.76) and time to neurocognitive progression (memory: HR=0.80, p=0.047, executive function: HR=0.74, p=0.028, all tests combined: HR=0.78, p=0.020). Conclusions: Motexafin gadolinium significantly prolonged time to neurologic progression and neurocognitive progression in NSCLC patients with brain metastases undergoing whole brain radiation therapy in a pooled analysis of 2 randomized phase III trials. [Table: see text] No significant financial relationships to disclose.
Should adult medulloblastoma patients at low risk receive adjuvant chemotherapy? Long-term results of a prospective study
Authors: Franceschi E. , Tosoni A. , Ermani M. , Blatt V. , Amistà P. , Sotti G. , Bartolini S. , Grosso D. , Pasetto L. M. , Brandes A. A. 
Published: March 2020

2018 Background: Due to the rarity of medulloblastoma (MB) in adults, the few studies available on this condition are retrospective, and the follow-up tends to be short. Furthermore, the different therapeutic strategies used in these patients makes it difficult to assess survival rates and prognostic factors. Methods: Between January 1989 and February 2001, a prospective phase II trial was performed to evaluate the efficacy of treatment for adults with medulloblastoma. Patients were completely staged with a neuroradiological examination of the brain and neuraxis and by CSF cytology, according to Chang’s staging system. Low risk patients received radiotherapy alone, while high risk patients were given 2 cycles of upfront chemotherapy followed by radiotherapy and adjuvant chemotherapy. The results of the preliminary analysis of this study at a median follow-up of 3.7 years are reported elsewhere. The present papers reports on the long- term results of the same trial. Results: After a median follow up of 7.6 years, among a total of 36 enrolled adults with medulloblastoma, overall progression free survival (PFS) and overall survival (OS) at 5 years were 72% (range 59% to 84%) and 75% (62% to 91%), respectively. No difference was found between low and high risk patients in terms of PFS and OS at 5 years: in low-risk patients the 5-year PFS was 80% (range, 59–100%) and the 5-year OS, 80% (range, 58 - 100%); in high-risk patients the 5-year PFS was 69% (range, 54 -89%) and the 5-year OS, 73% (range, 58 - 92%). Conclusions: A long-term follow-up is essential to evaluate the real impact of treatments in adult patients with MB. Since there is no significant difference between low-risk and high-risk patients for PFS and OS, the use of chemotherapy is also questionable in low-risk patients. No significant financial relationships to disclose.
Biochemical evidence of tumor response and measurable levels of the drug in glioblastoma tissue from patients treated with imatinib
Authors: Razis E. , Selviaridis P. , Fletcher J. , Labropoulos S. , Caprioli R. , Karkavelas G. , Zhu M. , Kalebic T. , Norris J. , Fountzilas G. 
Published: March 2020

2023 Background: Glioblastoma multiforme (GBM) carries a grave prognosis. There are phase I-II studies indicating that imatinib is active in GBM in pre-treated patients. To better understand the molecular basis of imatinib’s activity in this disease we performed a pharmacodynamic neoadjuvant study with imatinib in GBM. Methods: Patients underwent CT guided biopsy of their brain tumors. If diagnosed with GBM they were immediately treated with 7 days of imatinib 400mg po BID followed by either definitive surgery or, if that was not feasible, followed by re-biopsy. Corticosteroid dose was stable during this period and valproic acid was the only anti-epileptic drug allowed in order to avoid pharmacokinetic interaction with imatinib. Treatment after recovery was as per usual institutional policy. Pre and post treatment tissue specimens were analyzed by immunohistochemistry, proteomic technology and molecular biological methods. Pharmacokinetic studies were also performed. Results: Twenty patients were enrolled in 2 institutions with a median age of 64, of which 14 were male and 6 female. PS was 0 in 2, 1 in 9 and 2 in 9. Seventeen patients had pure GBM, 2 had mixed GBM with astrocytoma and one had anaplastic astrocytoma. Eighteen patients had stable disease on pre and post treatment MRI, one had progressed and one was not evaluable. Median survival was 6.2 months (1.1–18mo). Intact imatinib was quantified in the post treatment tissue specimens and correlations were made with serum imatinib levels per patient. No correlation was seen. Tissue specimens were analyzed by in situ MALDI mass spectroscopy and differential protein expression profiles were detected, when pre and post treatment specimens were compared. The identification of candidate proteins is ongoing. In 11 patients with evaluable, high-quality, matched pre and post imatinib biopsies, 4 had biochemical evidence of tumor response (decreased AKT or MAPK, or increased p27). In addition, 2 patients showed high-level EGFR activation, and one patient had high-level PDGFR activation. Conclusions: Treatment of GBM patients with imatinib results in measurable levels of the drug in the tumor. Potential indicators of biochemical response in a subset of patients were identified. No significant financial relationships to disclose.