bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise capacity in long-term survivors of pediatric cancer
Authors: Miller T. L. , Miller A. M. , Lopez-Mitnik G. , Somarriba G. , Lipsitz S. R. , Hinkle A. S. , Constine L. S. , Lipshultz S. E. 
Published: August 2020

10026 Background: Childhood cancer survivors may have premature symptomatic cardiovascular and noncardiovascular diseases that contribute to reduced capacity for physical activity. Controlled assessments of exercise capacity and identification of risk factors for reduced capacity in survivors are lacking. Methods: We assessed maximal myocardial oxygen consumption (VO2max; measure of exercise capacity) in survivors at least 4 years after diagnosis and sibling controls. We evaluated associations between VO2max and age, sex, treatments, cardiac structure and function, biomarkers, endocrine function, and physical activity. Results: Of 72 survivors (mean age, 22 y; range, 8.0 to 40 y) and 32 siblings (mean age, 20.2 y; range, 8 to 46 y), about half were male. The mean time since cancer diagnosis was 13.4 y (range, 4.5 to 31.6 y). In age- and sibling-pair adjusted analyses, VO2max was lower in survivors than siblings (males, 28.53 vs. 30.90 mL/kg/min, P = 0.08; females, 19.81 vs. 23.40 mL/kg/min, P = 0.03). In male survivors, older age (P = 0.01), higher percent body fat (P < 0.001) and high or low left ventricular (LV) mass Z-scores (P = 0.03) predicted lower VO2max. In females, older age (P < 0.001), methotrexate exposure (P = 0.01), and higher, but normal, LV load-dependent contractility (P = 0.02) predicted lower VO2max. Conclusions: Physical fitness for most participants in each group was poor, and was generally lower in survivors, particularly females. Older age, higher body fat, methotrexate exposure, and extremes of LV mass/function were associated with lower VO2max in survivors. Because physical activity can improve nutritional and cardiac conditions, survivors should be encouraged to engage in regular exercise with close medical monitoring. No significant financial relationships to disclose.
A longitudinal study of processing speed among children treated for medulloblastoma (MB), supratentorial primitive neuroectodermal tumor (SPNET), or atypical teratoid rhabdoid tumor (ATRT)
Authors: Palmer S. , Wallace D. , Bonner M. , Raggl R. , Chapieski L. , Janzen L. , Knight S. , Boyle R. , Armstrong C. , Gajjar A. 
Published: August 2020

10028 Background: Indicating a strong relationship to intelligence, processing speed parallels with the rate of knowledge acquisition. To further our understanding of the etiology of deficits in intellectual ability that continues to plague this group of children, the current study prospectively examined longitudinal changes in an underlying cognitive ability, processing speed. Methods: The study included 174 patients (median age at diagnosis = 9.0) enrolled on a multi-site protocol (SJMB03) for MB, SPNET or ATRT. Patients were treated with post-surgical risk-adapted craniospinal irradiation (CSI) followed by 4 cycles of high-dose chemotherapy (cyclophosphamide, cisplatin, vincristine) with stem cell support. High risk (HR, n = 55) patients received 36 - 39.6 Gy CSI and 3D conformal boost to the primary site to 55.8 –59.4 Gy. Average-risk (AR, n=119) patients received 23.4 Gy CSI, 3D conformal boost to the primary site to 55.8 Gy. Those who had posterior fossa syndrome were excluded (n = 26) resulting in 148 patients who completed 459 neuropsychological evaluations using the Woodcock Johnson Tests of Cognitive Abilities-III over a period of 0.03 –4.94 years postdiagnosis. Results: Multivariate modeling revealed a statistically significant decline in processing speed for those < 7 years of age at time of diagnosis (-3.83 points per year, p = 0.003). Those who were > 7 years at diagnosis did not experience a significant change (.86, NS). HR patients experienced greater declines (-.82) than those who were AR (-0.29), but neither slope was statistically significant. Interaction models revealed declines for those in the <7/AR group (-4.17, p = 0.003), and <7/HR group (-3.38, NS). Those >7/AR and >7/HR did not experience significant change (1.06 and 0.32, respectively). Conclusions: Young age at diagnosis is a prominent risk factor for processing speed impairment among survivors of pediatric embryonal tumors. Processing speed may also be among the first deficits to appear following treatment. This study represents the largest comparison of processing speed ability among patients treated for pediatric embryonal tumors with conventional or reduced dose CSI and adjuvant chemotherapy. No significant financial relationships to disclose.
Study of cisplatin, etoposide, bleomycin, and escalating dose cyclophosphamide therapy for children with high-risk germ cell tumors: A Children's Oncology Group report
Authors: Malogolowkin M. H. , Krailo M. , Frazier L. A. , Olson T. A. 
Published: August 2020

10035 Background: In the intergroup high-risk germ cell tumors (HR-GCT) study (CCG-8882/POG-9049) patients with extragonadal GCT treated with high-dose cisplatin, etoposide, and bleomycin (HD-PEB) had a 2 year-EFS of 84% versus 74% for those treated with standard PEB (PEB), suggesting that treatment intensification might be beneficial. The goal of this study was to establish the maximum tolerated dose (MTD) and toxicity profile of cyclophosphamide combined with PEB in untreated patients with HR-GCT. Methods: From July 2004 to August 2007, 19 eligible children and adolescents with stage III/IV extragonadal GCT received cisplatin 20 mg/m2/day × 5, etoposide 100 mg/m2/d × 5, bleomycin 15 mg/m2 on d1, and escalating doses of cyclophosphamide (1.2, 1.8 or 2.4 g/m2) on d1. DLT was defined as any grade 4 non-hematologic toxicity other than nausea and vomiting, fever and infection, and any non-hematologic grade 3 toxicity which had not reversed (< grade 2) within 28 days of treatment; or hematologic toxicity grade 3 or 4, which despite hematopoietic growth factor support, was not reversible within 28 days of treatment. Results: The toxicities reported were expected for this treatment regimen, protocol therapy was well tolerated and all 3 cyclophosphamide levels were feasible. Only 1 patient who had hyperglycemia was considered to have DLT by the institutional investigator. Fifteen of the 19 patients were removed from protocol therapy after 4 cycles of therapy; 11 were disease-free, 2 electively terminated protocol therapy, 1 patient was lost to follow-up, and 1 had progressive disease (PD). Four patients received 2 more cycles of C-PEB, of these 3 were disease-free and 1 had PD. The 2 year-EFS and OS were 71% (95% CI: 43–87%) and 88% (95% CI: 59–97%), respectively. Conclusions: The addition of cyclophosphamide to the standard PEB regimen is feasible and well tolerated at all dose levels used on this study. Due to the small sample size we cannot establish that the addition of cyclophosphamide to the standard PEB regimen is beneficial in increasing the EFS when compared to the standard PEB regimen. Further evaluation of this regimen is warranted. No significant financial relationships to disclose.
Childhood osteosarcoma: Evaluation of 94 cases. A single institution study
Authors: Ayan I. , Kebudi R. , Ozger H. , Yaman Agaoglu F. , Gorgun O. , Bilgic B. , Eralp L. , Dizdar Y. , Darendeliler E. 
Published: August 2020

10040 Background: Osteosarcoma is the most frequent bone tumor in children and adolescents. The aim of this study is to evaluate the demographic characteristics, therapy, and long term outcome of children with osteosarcoma in a single institution. Methods: Between January 1990 and December 2006, 94 children (53 male, 41 female) with a median age of 13 (5–16) years and a histopathologic diagnosis of osteosarcoma were treated with an institutional chemotherapy regimen comprising of 6 courses (3 pre-, 3 postoperatively) of epirubicin (90 mg/m2), cisplatin(100 mg/m2), and ifosfamide(2 g/m2 × 3 days) every 3 weeks. Results: The median follow-up time was 36 (2–219) months. 68 patients were alive at the time of analysis. 26 patients died; 20 of disease, 5 of toxicity, and 1 of second malignancy (acute myeloid leukemia). 90% of the patients had a limb salvage. 5 and 10 year OS for all patients were 64.7 % ( [95 % CI] 74.8–52.94 %) and 62.2 % (95 % CI 74.6–49.9 %), respectively. 5 and 10 year EFS for all patients was 51.8 % (95% CI 40.2–63.4 %). 5 and 10 year OS for nonmetastatic patients were 78.3 % (95% CI 66.9–89.7 %) and 75.1 %(95% CI 62.6–87.6), vs. 13.5 % 5 year OS for metastatic patients(95% CI 0–30.8 %) (p< 0.001). 5 and 10 year EFS for nonmetastatic patients was superior to those with metastatic disease [62.4 % (95% CI 49.9–79.9 %) vs. 6.9 % (95% CI 0–19.9 %)) (p<0.001). A total of 33 patients experienced relapse and/or progression at a median of 9 months (range 0–40 months). 10 year OS for 18 patients (11 metastatic at diagnosis) who progressed during preoperative chemotherapy was 13 % vs. 75 % for those who didnot have progressive disease (p< 0.001). The rate of histologically good response to preoperative chemotherapy was 64.5 %. Histologic response (<90 percent necrosis vs ≥90 percent) significantly correlated with 5 year EFS (31 % vs 67.6 %, p=0.023) but not with OS (57.7 % vs 76.5 %, p=0.13). Conclusions: The presence of metastases at diagnosis was the most significant characteristic influencing outcome. Our results demonstrate that the combination of epirubicin, cisplatin, and ifosfamide is an active and reasonably well-tolerated regimen for childhood osteosarcoma. No significant financial relationships to disclose.
Burkitt lymphoma in children: The Israel Society of Pediatric Hematology Oncology retrospective study
Authors: Weyl Ben Arush M. , Hersalis Eldar A. , Abrahami G. , Attias D. , Ben Barak A. , Dvir R. , Gabriel H. , Kapelushnik J. , Kaplinsky H. , Vilk-Revel S. 
Published: August 2020

10051 Background: From 2000 to 2005, the Israel Society of Pediatric Hematology Oncology studied the results of the FAB-LMB 96 protocol in children with B cell lymphoma. Methods: Eighty eight patients (pts) were eligible, 63 boys, 25 girls, median age was 8.9 years. Fifty patients (57%) were classified as burkitt lymphoma, 5 (5.7%) as burkitt-like lymphoma, 22 (25%) as diffuse large B cell (DLBC), 9 (10.2%) as burkitt leukemia. Initial disease sites included the abdomen in 43%, head and neck in 45%, mediastinum in 7%. Stage I: 9.1%, Stage II in 28.4%, stage III in 45.5%, stage IV in 17%. Five pts had bone marrow involvement (BM) alone, 5 pts CNS alone and 4 both CNS and BM. Five children were treated according to group A, 69 pts group B and 14 pts group C. Results: At a median follow up of 3 years, Kaplan Meier for EFS and OS for all pts was respectively 88.6%, 90.9%, group A, 100%,100%, group B: 90%, 93%, group C 79%, 79%. In group A: there were neither events nor deaths in this group, 6 patients relapsed in group B, among them 4 patients had died, tumor lysis syndrome in 3 patients, death of toxicity in 1 patient. In group C, 3 patients had relapsed and died, no death of toxicity. EFS for LDH less then twice was 96.4%, EFS for LDH more than twice was 73.3% (p = 0.002). OS according to primary site: bone and ovary (100%), head and neck (95%), abdomen (92%) and mediastinum (50%) (p = 0.003). All of the mediastinal tumors were of DLBC origin, but when comparing the DLBC to other histologies, no significant difference in outcome were found.(DLBC: 81.8%, other B line: 90.9%). The OS for Arab ethnic origin is 79.2%, OS for Jewish is 95.3% (p = 0.02). Conclusions: In nonresected mature B cell lymphoma of childhood and adolescence with no BM or CNS involvement, a 93% cure rate was achieved. Patients with primary DLBC mediastinal mass had a significantly reduced overall survival, indicating the need for a different therapeutic approach. No significant financial relationships to disclose.
Bone marrow infiltration in infants with disseminated neuroblastoma
Authors: De Bernardi B. , Sorrentino S. , Pasino M. , Gigliotti A. R. , Dau D. , Scuderi F. , Rosanda C. 
Published: August 2020

10056 Background: The INSS definition of stage 4S neuroblastoma allows a bone marrow infiltration (BMI) no greater than 10%. More extensive involvement is to be consider stage 4. However, the degree of BMI may be difficult to establish, since tumor cells in the marrow commonly aggregate in clumps. So far, no studies have specifically investigated this issue. In this study we have reviewed the bone marrow slides of infants with disseminated neuroblastoma enrolled between January 1998 and July 2008 in the Italian Neuroblastoma Registry. Methods: BMI was arbitrarily considered <10% when it consisted of a maximum of 5 tumor cell aggregates/slide in association to normal cellularity. Marrow was aspirated from iliac crests and slides were stained with Wright-Giemsa method. A minimum of 2 slides for aspirate were examined at low magnification. The same 2 hematologists (CR, MP) examined the slides independently along the study period, blind for clinical data. A third hematologist (FS) joined to perform the reviewing process. Results: Of 142 infants enrolled, we retrieved and reviewed bone marrow slides of 73. Before results of bone marrow study, 31 patients were defined as stage 4, and 42 as stage 4S. Following bone marrow study, 2 patients previously defined as stage 4S who had ≥10% BMI were moved to stage 4. The results of the revision are summarized ( Table ). Conclusions: In this study, only 2/42 infants with stage 4S clinical features had BMI ≥ 10% and were eventually labeled as stage 4. Whether chemotherapy for stage 4 is of advantage for these patients remains to be seen. [Table: see text] No significant financial relationships to disclose.
Incidence, detection, and management of cardiac metastasis in pediatric sarcoma patients
Authors: Hughes D. P. , Crutchley M. , Douglas W. I. , Munsell M. F. , Vaporciyan A. A. , Herzog C. , Tsai F. W. , Huh W. 
Published: August 2020

10060 Background: Sarcoma metastasizing to the heart is a difficult and complicated clinical problem, yet local control is feasible and effective for select patients with cardiac metastasis. Diligence is required to detect these lesions while still amenable to treatment, and echocardiogram remains the best tool for detecting cardiac disease. Methods: We reviewed all echocardiograms (1330) performed on 307 pediatric sarcoma patients treated at UT M. D. Anderson Cancer Center between 1997 and 2008. Measures of cardiac function and pathology (including size of ventricles and atria, function of ventricles and valves, presence of metastasis, and presence of pericardial effusion) were assigned numerical values. Fisher's exact test and the Wilcoxon rank-sum test compared clinical characteristics of patients with and without cardiac metastases. Results: The prevalence of cardiac metastases was 1.6% (5/307) with 95% confidence interval 0.5% to 3.8%. The presence of cardiac metastasis positively correlated with pericardial effusion (p = 0.001) and tricuspid valve insufficiency (p = 0.014). The probability of a patient with pericardial effusion having a cardiac metastasis was 28.6% (95% CI: 3.7%-71%). Of the 5 patients with documented sarcoma metastasis to the heart, 3 had widespread refractory disease, were given no cardiac-specific therapy, and rapidly died from disease. One patient who had widespread disease controlled with chemotherapy and radiation had open resection of 2 cardiac metastases which resulted in site-specific disease control for 6 months before succumbing to progressive extra-cardiac disease. Another patient had isolated cardiac metastasis, treated with open resection of 2 metastases followed by adjuvant chemotherapy, and has been without recurrent cardiac metastases for 5 years and 9 months. Conclusions: Durable local control for sarcoma metastasizing to the heart is possible and effective for select patients. Pericardial effusion merits evaluation for potential associated cardiac metastasis. Echocardiogram monitoring of sarcoma patients remains important, and should include screening for possible cardiac metastasis. No significant financial relationships to disclose.
Efficacy and safety of radioiodine in the treatment of disseminated differentiated thyroid cancer (DTC) in children
Authors: Handkiewicz-Junak D. , Roskosz J. , Kropinska A. , Kozielski J. , Krzywiecki A. , Krajewska J. , Krajewska J. , Puch Z. , Olczyk T. , Jarzab B. 
Published: August 2020

10065 Background: Distant metastases, mainly to lung are diagnosed in about 20% of children with DTC. At present radioiodine is the treatment of choice in that case. However, it can results in massive lung fibrosis as was showed in historical groups of patients.The aim of this retrospective study was to evaluate results of radioiodine therapy in children and its long-term safety. Methods: From 235 children (median age 13.9) diagnosed either with papillary (82%) or follicular cancer (18%), 42 (17.9%) had lung, and 2 (9%) bone metastases (median time of observation 105 months). All were treated with radioiodine (accumulated activities 100 to 950 mCi). Treatment results were evaluated by means of scintigraphic, radiological, and biochemical examinations. 28 (67%) of the children were lately re-evaluated with high resolution CT, ultrasound, biochemistry, and spirometry. Results: In most children, 29/44 (66%), distant metastases were diagnosed in radioiodine scan while radiological examinations were normal. Complete scintigraphic and radiological remission was achieved in 38 (86%) children. In all children there was a decrease in thyroglobulin serum concentration after radioiodine therapy. However, it normalized at the last radioiodine treatment only in 13 (29%) cases. During follow-up Tg continued to decrease and at the last stimulated Tg evaluation it was < 10 ng/ml in 28 (64%) patients. In 5/28 (18%) of the children with lung metastases some small foci of focal lung fibrosis were diagnosed with CT. However, comparable percentage of focal fibrosis was observed in DTC children without lung metastases. Also the preliminary results didn't show an increased rate of abnormal spirometry results. Conclusions: Complete remission of distant metastases can be achieved in about 85% of children with DTC treated with radioiodine. This therapy is safe and does not cause any increased risk of lung fibrosis even in children treated with repeated courses of radioiodine. No significant financial relationships to disclose.
Exploratory subset analysis according to prior endocrine treatment of two randomized phase II trials comparing gefitinib (G) with placebo (P) in combination with tamoxifen (T) or anastrozole (A) in hormone receptor-positive (HR+) metastatic breast cancer (MBC)
Authors: Cristofanilli M. , Schiff R. , Valero V. , Iacona R. , Yu J. , Speake G. , Smith I. , Osborne C. K. 
Published: August 2020

1014 Background: Preclinical and clinical data suggest that increased EGFR and HER-2 activity contribute to acquired resistance to endocrine therapy. Strata of two clinical trials recently showed that the addition of G to T or A in HR+ MBC prolonged progression free-survival (PFS). Certain preclinical data also suggested that G should be combined with T or A from the start of endocrine therapy rather than waiting for resistance to develop. To examine this clinically a post hoc analysis compared the subsets of patients (pts) who had received prior endocrine therapy (may have already upregulated HER receptors) to those that were endocrine therapy naïve (not yet upregulated HER receptors). Methods: One trial evaluated G (250 mg/day orally) + A (1 mg/day orally) versus A+P ( NCT00077025 ) and one trial evaluated G (250 mg/day orally) + T (20 mg/day orally) versus T+P ( NCT00229697 ). Post hoc analysis of PFS was performed in two pt subgroups; previously treated with endocrine therapy (ET) and endocrine naïve (EN). The PFS HR and associated 95% CI and p-value for G relative to P were estimated using the Cox proportional hazards model along with interaction test for treatment by subset. Results: In the ET subgroup of the G+A versus A+P study, 31 PFS events were reobserved in 51 pts (hazard ratio [HR] 0.65 95% CI 0.32, 1.33; median PFS: G+A 11.2 mo, A+P 7.1 mo). In the EN subgroup, 23 PFS events were reobserved in 42 pts (HR 0.39, 95% CI 0.16, 0.97; median PFS: G+A 20.2 mo, A+P 8.4 mo). The interaction test p-value was 0.28. In the ET subgroup of the G+T versus T+P study, 95 PFS events were reobserved in 131 pts (HR 1.22, 95% CI 0.81, 1.86; median PFS: G+T 9.4 mo, T+P 10.9 mo). In the EN subgroup, 106 PFS events were reobserved in 158 patients (HR 0.78, 95% CI 0.52, 1.15; median PFS: G+T 12.1 mo, T+P 8.9 mo). The interaction test p-value was 0.13. Conclusions: The EN pt subgroups of both trials demonstrated prolonged PFS when G was combined with A or with T compared with A or T alone, respectively. A further prospective clinical trial of EGFR inhibition combined with endocrine therapy in EN pts with HR+ MBC is warranted on the basis of these findings. [Table: see text]
A phase II study of trastuzumab-DM1 (T-DM1), a HER2 antibody-drug conjugate (ADC), in patients (pts) with HER2+ metastatic breast cancer (MBC): Final results
Authors: Vogel C. L. , Burris H. A. , Limentani S. , Borson R. , O'Shaughnessy J. , Vukelja S. , Agresta S. , Klencke B. , Birkner M. , Rugo H. 
Published: August 2020

1017 Background: T-DM1 is an ADC that combines the biological activity of trastuzumab (T) with targeted delivery of a potent antimicrotubule agent, DM1, to HER2-expressing cancer cells. In a phase I study, T-DM1 was administered IV q3w to pts with HER2+ MBC who had progressed on T + chemotherapy. T-DM1 was well-tolerated at the maximum tolerated dose (MTD) of 3.6 mg/kg, with no reports of cardiac toxicity. The confirmed objective response rate (ORR) for the 9 pts with measurable disease treated at the MTD was 44%. The phase II study described here further assesses tolerability and activity of T-DM1. Methods: This was a multi-institutional, open-label, single-arm phase II study, to enroll 100 pts. All eligible pts had progressed on HER2-directed therapy and had received chemotherapy in the metastatic setting. T-DM1 was administered at 3.6 mg/kg IV q3w. Primary objectives were assessment of ORR and of safety and tolerability. Results: As of the August 29, 2008, data-cut, 112 patients had enrolled, with baseline median age 54.5 (range 33–82); ECOG PS 2 or 3, 80%; 68.7% with > 3 sites of metastatic disease; median 3 (range 1–14) prior chemotherapy agents for metastatic disease, median 76.3 weeks prior T, and 55.4% with previous lapatinib. Due to limited F/U, the median number of T-DM1 cycles received was 5 (range 1–16), and 19 of the 107 efficacy evaluable patients had only one post-baseline tumor assessment. Fifty-six pts had discontinued study treatment. With a median follow-up of 4.4 mos, there were 42 (39.3%) ORs (CR or PR), 29 (27.1%) of which have been confirmed by follow-up (F/U) imaging. Among the subgroup of pts who had either >6 months F/U or had discontinued from the study at any time (n = 76) there were 33 ORs (43.4%), 29 (38.2%) of which were confirmed by F/U imaging. The most common grade 3–4 AE was thrombocytopenia (7.1%). Updated data will be presented at the meeting, including updated ORR, 6-month clinical benefit rate, ORR by independent review, progression-free survival, and duration of response. Conclusions: T-DM1 has single-agent activity in pts with previously treated, HER2+ MBC, and is well tolerated at the recommended phase II dose. [Table: see text]