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ABSTRACT: OBJECTIVE: To ascertain prevalence of peripheral sensory and motor neuropathy; to evaluate impairments in relation to function. DESIGN: St. Jude Lifetime Cohort Study, a clinical follow-up study designed to evaluate adverse late effects in adult survivors of childhood cancer. SETTING: St. Jude Children's Research Hospital (SJCRH). PARTICIPANTS: Eligibility required treatment for an extracranial solid malignancy between 1962 and 2002, age ≥18 years, ≥10 years post-diagnosis, no history of cranial radiation. 531 survivors were included in the evaluation: median age 32 years, median time from diagnosis 25 years. Interventions: Not applicable. MAIN OUTCOME MEASURES: Primary exposure measures were cumulative doses of vinca-alkaloid and platinum-based chemotherapies. Survivors with scores ≥ 1 on the sensory subscale of the modified Total Neuropathy Score were classified with prevalent sensory impairment. Those with sex-specific Z-scores of ≤-1.3 for dorsiflexion strength were classified with prevalent motor impairment. Participants completed the 6-minute walk test (endurance), the timed up and go test (mobility), and the sensory organization test (balance). RESULTS: The prevalence of sensory and motor impairment was 20% and 17.5%, respectively. Vinca-alkaloid exposure was associated with an increased risk of motor impairment (adjusted odds ratio (OR)=1.66, 95% Confidence Interval (CI): 1.04-2.64) without evidence for a dose response. Platinum exposure was associated with increased risk of sensory impairment (adjusted OR= 1.62, 95% CI: 0.97-2.72) without evidence of a dose response. Sensory impairment was associated with poor endurance (OR=1.99, 95% CI: 0.99-4.00) and mobility (OR=1.65, 95% CI: 0.96-2.83). CONCLUSION: Vincristine and cisplatin exposure may increase risk for long-term motor and sensory impairment, respectively. Survivors with sensory impairment are at increased risk for functional performance limitations.
Archives of physical medicine and rehabilitation 03/2013; · 2.18 Impact Factor
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Daniel M Green,
Liang Zhu,
Nan Zhang,
Charles A Sklar,
Raymond W Ke,
William H Kutteh,
James L Klosky, Sheri L Spunt,
Monika L Metzger,
Fariba Navid,
Deokumar Srivastava,
Leslie L Robison,
Melissa M Hudson
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ABSTRACT: PURPOSEMany male survivors of childhood cancer are at risk for azoospermia. Although both the levels of follicle-stimulating hormone (FSH) and inhibin B are correlated with sperm concentration, their ability to predict azoospermia in survivors of childhood cancer remains uncertain.Patients And methodsSemen analysis was performed and serum levels of FSH and inhibin B were measured in 275 adult male survivors of childhood cancer who had received gonadotoxic therapy. Receiver operating characteristic (ROC) analysis was performed to determine the optimal inhibin B and FSH values for identifying patients with azoospermia. The patient sample was divided into a learning set and a validation set. Sensitivity, specificity, and positive and negative predictive value were calculated.ResultsInhibin B was dichotomized as ≤ 31 ng/L or more than 31 ng/L and FSH was dichotomized as ≤ 11.5 mIU/mL or more than 11.5 mIU/mL based on results of the ROC analysis. Using these values, the specificity of the serum level of inhibin B for identifying azoospermic survivors was 45.0%, and the positive predictive value was 52.1%. The specificity for FSH was 74.1%, and the positive predictive value was 65.1%. CONCLUSION
Neither serum inhibin B nor FSH is a suitable surrogate for determination of sperm concentration in a semen sample. Young men and their physicians should be aware of the limitations of these measures for assessment of fertility potential.
Journal of Clinical Oncology 02/2013; · 18.37 Impact Factor
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ABSTRACT: Children with solid tumors, most of which are malignant, have an excellent prognosis when treated on contemporary regimens. These regimens, which incorporate chemotherapeutic agents and treatment modalities used for many decades, have evolved to improve relapse-free survival and reduce long-term toxicity. This review discusses the evolution of the treatment regimens employed for management of the most common solid tumors, emphasizing the similarities between contemporary and historical regimens. These similarities allow the use of historical patient cohorts to identify the late effects of successful therapy and to evaluate remedial interventions for these adverse effects. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
Pediatric Blood & Cancer 02/2013; · 1.89 Impact Factor
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Stephen X Skapek,
James R Anderson,
D Ashley Hill,
David Henry, Sheri L Spunt,
William Meyer,
Simon Kao,
Fredric A Hoffer,
Holcombe E Grier,
Douglas S Hawkins,
R Beverly Raney
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ABSTRACT: BACKGROUND: Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children's Oncology Group. PROCEDURES: Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging. RESULTS: Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10-18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23-0.48) and 96%, respectively. All three deaths were due to progressive DT. CONCLUSIONS: Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.
Pediatric Blood & Cancer 12/2012; · 1.89 Impact Factor
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ABSTRACT: In the US, approximately 850-900 children are diagnosed each year with soft tissue sarcomas (STS). Key findings from recent Children's Oncology Group (COG) clinical trials include safe reduction in therapy for low risk rhabdomyosarcoma (RMS), validation of FOXO1 fusion as a prognostic factor, a modest improvement in outcome for high-risk RMS, and a biologically designed non-cytotoxic therapy for pediatric desmoid tumor. Planned Phase 2 trials include targeted agents for VEGF/PDGF, mTOR, and IGF-1R for children with RMS and VEGF for children with non-RMS STS (NRSTS). For RMS, COG Phase 3 trials potentially will explore VEGF/mTOR inhibition or chemotherapy interval compression. For NRSTS, a COG Phase 3 trial will explore VEGF inhibition. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.
Pediatric Blood & Cancer 12/2012; · 1.89 Impact Factor
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ABSTRACT: BACKGROUND: Over the past decade, PET-CT has been used to assess rhabdomyosarcoma (RMS) in children. However, the role of PET-CT in staging RMS is unknown. PROCEDURE: Thirty subjects with RMS, median age 7.3 years, underwent PET-CT before therapy. PET-CTs and conventional imaging (CI) were independently reviewed by two radiologists and two nuclear medicine physicians to determine the presence of metastases. Accuracy, sensitivity, and specificity of PET-CT for detecting metastases were compared to CI using biopsy and clinical follow-up as reference standards. Maximum standardized uptake values (SUV(max) ) of primary tumors, lymph nodes, and pulmonary nodules were measured. RESULTS: Primary tumors had an average SUV(max) of 7.2 (range, 2.5-19.2). Accuracy rates for 17 subjects with nodal disease were 95% for PET-CT and 49% for CI. PET-CT had 94% sensitivity and 100% specificity for nodal disease. Of seven pulmonary nodules detected by CI, three were not identified by PET-CT, two were indeterminate, and one was malignant with a SUV(max) (3.4) > twice that of benign nodules. Two subjects had bone disease; both were identified by PET-CT but only one by CI. Four subjects had bone marrow disease, two had positive PET-CTs but none had positive CI. Two subjects had soft tissue metastases detected by PET-CT but not CI. CONCLUSIONS: PET-CT performed better than CI in identifying nodal, bone, bone marrow, and soft tissue disease in children with RMS. CI remains essential for detection of pulmonary nodules. We recommend PET-CT for staging of children with RMS. CI with Tc(99m) bone scan can be eliminated. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.
Pediatric Blood & Cancer 12/2012; · 1.89 Impact Factor
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ABSTRACT: PURPOSE: Our objective was to evaluate the association between low bone mineral density (BMD) and incidental renal stones among long-term survivors of childhood acute lymphoblastic leukemia (ALL). METHODS: Adult participants who were 10+ years from their childhood ALL diagnosis and members of the St. Jude Lifetime Cohort study were recruited between December 2007 and March 2011. During their risk-based medical evaluations, they underwent quantitative computed tomography (QCT) to evaluate BMD. Incidental renal stones were identified by radiologists' review of axial QCT source images. Demographic and dietary information were abstracted from health surveys and the Block Food Frequency questionnaire, respectively. The multivariable logistic regression model was used for analysis. RESULTS: At a median of 26.1 years from diagnosis, BMD Z scores were ≤-2 in 34 of 662 (5.2 %) and renal stones detected in 73 of 662 (11 %) participants. Adjusted for age, renal radiation, dietary vitamin D, gender, and body mass index, when compared to those with BMD Z scores ≥0, the risk of renal stones was increased among those with BMD Z scores ≤-2 (odds ratio [OR], 2.92; 95 % confidence interval [CI] 1.14-7.48). Risk of renal stones significantly increased for older age (45-54 vs.18-24 years; OR, 3.70; 95 % CI 1.11-12.35) whereas the risk was higher but nonsignificant for >141.5 IU (sample median) daily intake of vitamin D (OR, 1.64; 95 % CI 0.98-2.75). CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Older ALL survivors with BMD Z scores ≤-2 are at risk for renal stones and should be counseled so that appropriate follow-up care can be provided for those among whom renal stones are detected.
Journal of Cancer Survivorship 09/2012; · 2.63 Impact Factor
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ABSTRACT: In this single-site study, we evaluated the feasibility of a parent-clinician communication intervention designed to: identify parents' rationale for the phase I, do-not-resuscitate (DNR), or terminal care decision made on behalf of their child with incurable cancer; identify their definition of being a good parent to their ill child; and provide this information to the child's clinicians in time to be of use in the family's care.
Sixty-two parents of 58 children and 126 clinicians participated. Within 72 hours after the treatment decision, parents responded to 6 open-ended interview questions and completed a 10-item questionnaire about the end-of-life communication with their child's clinicians. They completed the questionnaire again two to three weeks later and responded to three open-ended questions to assess the benefit:risk ratio of their study participation three months after the intervention. Clinicians received the interview data within hours of the parent interview and evaluated the usefulness of the information three weeks later.
All preestablished intervention feasibility criteria were met; 77.3% of families consented; and in 100% of interventions, information was successfully provided individually to 3 to 11 clinicians per child before the child died. No harm was reported by parents as a result of participating; satisfaction and other benefits were reported. Clinicians reported moderate to strong satisfaction with the intervention.
The communication intervention was feasible within hours of decision making, was acceptable and beneficial without harm to participating parents, and was acceptable and useful to clinicians in their care of families.
Journal of palliative medicine 06/2012; 15(8):916-22. · 1.84 Impact Factor
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Ching-Hon Pui,
Deqing Pei,
Alberto S Pappo,
Scott C Howard,
Cheng Cheng,
John T Sandlund,
Wayne L Furman,
Raul C Ribeiro, Sheri L Spunt,
Jeffrey E Rubnitz, [......],
Melissa M Hudson,
Larry E Kun,
Thomas E Merchant,
Mehmet Kocak,
Alberto Broniscer,
Monika L Metzger,
James R Downing,
Wing Leung,
William E Evans,
Amar Gajjar
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ABSTRACT: Treatment outcome for black patients with cancer has been significantly worse than for their white counterparts. We determined whether recent improved treatment had narrowed the gap in outcome between black and white pediatric patients.
In a parallel comparison, we analyzed survival by disease category between black and white patients with childhood cancer registered in one of the 17 cancer registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program or treated at St Jude Children's Research Hospital, which provides comprehensive treatment to all patients regardless of their ability to pay, from 1992 to 2000 and from 2001 to 2007.
Analysis of the SEER data indicated that in both study periods, black patients had significantly poorer rates of survival than did white patients, with the exception of a few types of cancer. Despite significantly improved treatment outcomes for patients who were treated from 2001 to 2007, the racial difference in survival has actually widened for acute myeloid leukemia and neuroblastoma. By contrast, in the cohorts treated at St Jude Children's Research Hospital, there were no significant differences in survival between black and white patients in either study period, regardless of the cancer type. Importantly, the outcome of treatment for acute lymphoblastic leukemia, acute myeloid leukemia, and retinoblastoma has improved in parallel for both races during the most recent study period.
With equal access to comprehensive treatment, black and white children with cancer can achieve the same high cure rates.
Journal of Clinical Oncology 04/2012; 30(16):2005-12. · 18.37 Impact Factor
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ABSTRACT: A phase II study of temsirolimus was conducted in children and adolescents with high-grade glioma, neuroblastoma or rhabdomyosarcoma.
Temsirolimus 75 mg/m(2) was administered once weekly until disease progression or intolerance. Using the Simon 2-stage design, further enrolment in each disease cohort required ≥ 2 objective responses within the first 12 weeks for the first 12 evaluable patients (those who received ≥ 3 temsirolimus doses).
Fifty-two heavily pretreated patients with relapsed (12%) or refractory (88%) disease, median age 8 years (range 1-21 years), were enroled and treated. One patient with neuroblastoma achieved confirmed partial response within the first 12 weeks; thus, none of the 3 cohorts met the criterion for continued enrolment. Disease stabilisation at week 12 was observed in 7 of 17 patients (41%) with high-grade glioma (5 diffuse pontine gliomas, 1 glioblastoma multiforme and 1 anaplastic astrocytoma), 6 of 19 (32%) with neuroblastoma and 1 of 16 (6%) with rhabdomyosarcoma (partial response confirmed at week 18). In the three cohorts, median duration of stable disease or better was 128, 663 and 75 d, respectively. The most common treatment-related adverse events were thrombocytopaenia, hyperlipidaemia and aesthenia. Pharmacokinetic findings were similar to those observed in adults.
Temsirolimus administered weekly at the dose of 75 mg/m(2) did not meet the primary objective efficacy threshold in children with high-grade glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable disease merits further evaluation in combination therapy.
European journal of cancer (Oxford, England: 1990) 01/2012; 48(2):253-62. · 4.12 Impact Factor
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ABSTRACT: Not knowing about a child's death can result in poor quality of care coordination among staff and poor quality bereavement care for families. The purpose of this project was to create, implement, and evaluate an automated Patient Death Notification policy and procedure (PDNPP).
Baseline and follow-up surveys of clinical staff.
Implementation of a PDNPP that created an automated, systematic process for staff notification of patient deaths.
Ninety-six percent of the staff rated the PDNPP as a significant improvement; 91% reported being "very" or "somewhat" satisfied with the PDNPP, whereas only 44% of the staff were satisfied with the process at baseline. CONCLUSIONS/LESSONS LEARNED: Implementation of an automated PDNPP was feasible and improved staff satisfaction about how they were informed of patient deaths. Staff also reported being notified about patient deaths more quickly, performing their jobs more efficiently, being able to avoid doing something that might upset the deceased patient's family, and being able to better provide support to bereaved families.
Journal of pain and symptom management 11/2011; 42(5):652-6. · 2.42 Impact Factor
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ABSTRACT: The aim of this study was to retrospectively analyze the clinical presentation, histology, treatment, and outcomes of children with vaginal tumors who were treated at a single institution.
A retrospective review of medical records and pathologic materials of all children with vaginal tumors treated at St Jude Children's Research Hospital between 1970 and 2009 was conducted.
Eighteen patients (median age, 3.7 years; range, 0.1-15 years) were identified. Three different histologies were found: rhabdomyosarcoma (RMS; n = 13), germ cell tumor (n = 3), and clear cell adenocarcinoma (n = 2). Bleeding or blood-tinged discharge was the most common clinical presentation (66%), followed by a protruding mass (39%). Vaginal and uterine salvage was 44.4% (8 of 18 patients). Thirteen patients (72.2%) remain disease-free, with a median follow-up of 23.2 years (range, 2-39 years). Four patients (22.2%) died of disease progression (1 RMS, 2 germ cell tumor, and 1 clear cell adenocarcinoma), and 1 patient with RMS died of colon cancer 12 years after the primary diagnosis had been made.
Vaginal tumors are extremely rare in the pediatric population. Early recognition of symptoms like bleeding and a protruding vaginal mass may prevent morbidity and mortality. Our findings confirm the good prognosis of vaginal RMS.
Journal of Pediatric Surgery 11/2011; 46(11):2071-5. · 1.45 Impact Factor
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Cancer 10/2011; 118(12):3002-9. · 4.77 Impact Factor
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Megan S Motosue,
Liang Zhu,
Kumar Srivastava,
Dennis C Stokes,
Melissa M Hudson,
Valerie McPherson,
Saumini Srinivasan,
Matthew J Krasin,
Daniel M Green, Sheri L Spunt,
Hiroto Inaba
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ABSTRACT: Although whole lung irradiation is used to treat pulmonary metastases of pediatric solid malignancies, few studies have addressed its long-term pulmonary consequences.
The authors conducted a retrospective study of longitudinal changes in 171 pulmonary function tests (PFTs) and their relation with clinical features in 48 survivors of pediatric malignant solid tumors treated with whole lung irradiation.
Although active respiratory symptoms were seen in only 9 patients (18.8%), abnormalities in forced vital capacity (FVC; 58.3%), forced expiratory volume in 1 second (FEV(1) ; 64.6%), total lung capacity (TLC; 72.9%), and diffusion capacity of the lung for carbon monoxide corrected for hemoglobin (DLCO(corr) ; 70.8%) were common. At a median follow-up of 9.7 years after whole lung irradiation, FVC, FEV(1) , and TLC significantly declined longitudinally (P = .04, .03, and .02, respectively). Focal pulmonary boost irradiation was significantly associated with abnormal FEV(1) /FVC (P = .03), forced expiratory flow between 25% and 75% forced vital capacity (P = .005), residual volume (RV; P = .005), and RV/TLC (P = .002). Ten patients had baseline PFTs, and FVC, FEV(1) , TLC, and DLCO(corr) worsened immediately after radiation, followed by transient improvement but subsequent decline. Thirteen of 32 (40.6%) patients aged >18 years were smokers.
Pulmonary dysfunction was prevalent after whole lung irradiation and worsened over time, although most patients were asymptomatic. Boost irradiation impaired pulmonary function, and a significant proportion of patients were smokers. Further studies are planned to assess the predictors and clinical consequences of progressive PFT abnormalities and to evaluate educational interventions.
Cancer 07/2011; 118(5):1450-6. · 4.77 Impact Factor
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ABSTRACT: Soft tissue sarcomas (STS) are a heterogeneous group of mesenchymal malignancies that occur throughout the lifespan. The impact of age on disease features and outcome is unclear.
We analyzed the clinical features and outcome of all STS cases registered between 1973 and 2006 in the SEER database.
There were 48,012 cases that met the selection criteria. Individuals less than 20 years of age represented 5.6%, with rhabdomyosarcoma being the most common subtype. In adults, the most common types were Kaposi sarcoma, fibrohistiocytic tumors, and leiomyosarcoma. Rhabdomyosarcoma was the only entity with a median age <20 years. Male predominance (male/female of 1.5:1) was noticed for almost all types of STS, except for alveolar soft part sarcoma and leiomyosarcoma. Tumor stage was similar across different age groups. Younger patients (<50 years) had significantly better survival than older patients (88.8 ± 0.2% vs. 40 ± 0.3%, P < 0.001), but for most histologies the survival decline with advancing age was gradual and did not occur abruptly at the onset of adulthood. The decline in survival with advancing age was particularly significant for rhabdomyosarcoma.
With few exceptions, the clinical features of STS are similar in children and adults. However, individuals over 50 years of age have an inferior survival.
Pediatric Blood & Cancer 07/2011; 57(6):943-9. · 1.89 Impact Factor
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ABSTRACT: Patients aged >10 years with rhabdomyosarcoma have an inferior outcome compared with patients ages 1 to 9 years, which may be explained by toxicities (adverse events [AEs]) that result in chemotherapy dose reductions.
AEs observed during 1 of 3 randomized chemotherapy regimens (vincristine, dactinomycin, and cyclophosphamide [VAC]; vincristine, dactinomycin, and ifosfamide [VAI]; or vincristine, ifosfamide, and etoposide [VIE]) in the Fourth Intergroup Rhabdomyosarcoma Study were recorded. The incidence of toxicities by age and treatment regimen was determined. The odds of developing AEs in a particular age group (ages 5-9 years, 10-14 years, and 15-20 years) were compared with the odds in the control group of patients ages 1 to 4 years.
In total, 657 patients were eligible for analysis. The estimated 5-year event-free survival rates were 78%, 83%, 67%, and 58% for the groups ages 1 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 20 years, respectively. Patients ages 15 to 20 years experienced less neutropenia (odds ratio [OR], 0.43; P < .0001), thrombocytopenia (OR, 0.41; P < .0001), anemia (OR, 0.34; P < .0001), and infection (OR, 0.41; P < .0001) compared with younger patients, although they received similar amounts of chemotherapy. In contrast, peripheral nervous system toxicity was higher in adolescents aged >10 years (OR, 4.18; P < .0001). Females experienced more neutropenia (OR, 1.28; P = .05) and thrombocytopenia (OR, 1.26; P = .06) compared with males.
Adolescents who received treatment for rhabdomyosarcoma experienced significantly less hematologic toxicity and more peripheral nervous system toxicity compared with younger children despite receiving similar amounts of chemotherapy. Although outcomes were inferior in adolescents, it was unclear whether the differences in toxicity observed in the current study had an impact on outcome. The authors concluded that future studies examining the age-related and sex-related differences in pharmacokinetics of chemotherapy are necessary.
Cancer 07/2011; 118(4):1130-7. · 4.77 Impact Factor
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Sheri L Spunt,
Stephan A Grupp,
Terry A Vik,
Victor M Santana,
David J Greenblatt,
Jill Clancy,
Anna Berkenblit,
Mizue Krygowski,
Revathi Ananthakrishnan,
Joseph P Boni,
Richard J Gilbertson
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ABSTRACT: To determine dose-limiting toxicities, maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of weekly intravenous temsirolimus, a mammalian target of rapamycin (mTOR) signaling pathway inhibitor, in pediatric patients with recurrent or refractory solid tumors.
Cohorts of three to six patients 1 to 21 years of age with recurrent or refractory solid tumors were treated with a 1-hour intravenous infusion of temsirolimus weekly for 3 weeks per course at one of four dose levels: 10, 25, 75, or 150 mg/m(2). During the first two courses, pharmacokinetic and pharmacodynamic evaluations (phosphorylation of S6, AKT, and 4EBP1 in peripheral-blood mononuclear cells) were performed.
Dose-limiting toxicity (grade 3 anorexia) occurred in one of 18 evaluable patients at the 150 mg/m(2) level, which was determined to be tolerable, and an MTD was not identified. In 13 patients evaluable for response after two courses of therapy, one had complete response (CR; neuroblastoma) and five had stable disease (SD). Four patients (three SDs + one CR) remained on treatment for more than 4 months. The sum of temsirolimus and sirolimus areas under the concentration-time curve was comparable to values in adults. AKT and 4EBP1 phosphorylation were inhibited at all dose levels, particularly after two courses.
Weekly intravenous temsirolimus is well tolerated in children with recurrent solid tumors, demonstrates antitumor activity, has pharmacokinetics similar to those in adults, and inhibits the mTOR signaling pathway in peripheral-blood mononuclear cells. Further studies are needed to define the optimal dose for use in combination with other antineoplastic agents in pediatric patients.
Journal of Clinical Oncology 06/2011; 29(21):2933-40. · 18.37 Impact Factor
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Melissa M Hudson,
Kirsten K Ness,
Vikki G Nolan,
Gregory T Armstrong,
Daniel M Green,
E Brannon Morris, Sheri L Spunt,
Monika L Metzger,
Kevin R Krull,
James L Klosky,
Deo Kumar Srivastava,
Leslie L Robison
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ABSTRACT: To facilitate prospective medical assessment of adults surviving pediatric malignancies and advance knowledge about long-term childhood cancer survivor health, St. Jude Children's Research Hospital (SJCRH) is establishing a lifetime cohort of survivors.
Eligibility criteria for inclusion in the St. Jude Lifetime Cohort (SJLIFE) study include: (1) diagnosis of childhood malignancy treated at SJCRH; (2) survival ≥ 10 years from diagnosis; and (3) current age ≥ 18 years. Three levels of participation are offered: (1) comprehensive evaluation on SJCRH campus; (2) limited home evaluation; or (3) completion of health surveys only. A systematic recruitment structure based upon blocks of 50 patients initially focused on leukemia and lymphoma survivors and patients eligible for pilot studies.
As of January 1, 2010, 1,625 (42%) of 3,900 eligible ≥ 10-year survivors have been contacted. Among the first 1,000 potentially eligible survivors selected for recruitment, 971 were subsequently confirmed to fulfill eligibility criteria. To date, 898/971 (92.5%) have been successfully contacted of whom 825 (91.8%) have agreed to participate. Among participants, 88.6% agreed to comprehensive medical evaluation, 0.4% limited local evaluation, and 11.0% survey only. Anticipated minimum overall participation rate for medical evaluation is 75.3% (731/971). Comparison of those contacted who agreed versus declined to participate revealed a greater proportion of males who declined participation (P = 0.001).
Early results of the SJLIFE study support its feasibility to recruit aging childhood cancer survivors to research investigations evaluating late health outcomes by medical assessments.
Pediatric Blood & Cancer 05/2011; 56(5):825-36. · 1.89 Impact Factor
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ABSTRACT: The purpose of this article is to summarize the literature that documents the long-term impact of cancer treatment modalities on pulmonary function among survivors of cancer and to identify potential areas for further research.
Systematic reviews of clinical trials, observational studies, case series, and review articles were conducted. Articles were limited to the studies that discussed pulmonary toxicity or late effects among pediatric cancer survivors and to follow-up investigations that were conducted a minimum of 2 years after completion of cancer-related treatment or 1 year after hematopoietic stem cell transplant.
Sixty publications (51 clinical studies/reports and nine reviews) published from January 1970 to June 2010 in PubMed met the inclusion criteria. Data showed an association between radiotherapy, alkylating agents, bleomycin, hematopoietic stem cell transplant, and thoracic surgery and pulmonary toxicity, as well as possible interactions among these modalities.
Pulmonary toxicity is a common long-term complication of exposure to certain anticancer therapies in childhood and can vary from subclinical to life threatening. Pulmonary function and associated loss of optimal exercise capacity may have adverse effects on long-term quality of life in survivors. Lung function diminishes as a function of normal aging, and the effects of early lung injury from cancer therapy may compound these changes. The information presented in this review is designed to provide a stimulus to promote both observational and interventional research that expands our knowledge and aids in the design of interventions to prevent or ameliorate pulmonary late effects among survivors of childhood cancer.
Chest 03/2011; 140(4):881-901. · 5.25 Impact Factor
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ABSTRACT: Rhabdomyosarcoma, a neoplasm composed of skeletal myoblast-like cells, represents the most common soft tissue sarcoma in children. The application of intensive chemotherapeutics and refined surgical and radiation therapy approaches have improved survival for children with localized disease over the past 3 decades; however, these approaches have not improved the dismal outcome for children with metastatic and recurrent rhabdomyosarcoma. Elegant studies have defined the molecular mechanisms driving skeletal muscle lineage commitment and differentiation, and the machinery that couples differentiation with irreversible cell proliferation arrest. Further, detailed molecular analyses indicate that rhabdomyosarcoma cells have lost the capacity to fully differentiate when challenged to do so in experimental models. We review the intersection of normal skeletal muscle developmental biology and the molecular genetic defects in rhabdomyosarcoma with the underlying premise that understanding how the differentiation process has gone awry will lead to new treatment strategies aimed at promoting myogenic differentiation and concomitant cell cycle arrest.
Current Topics in Developmental Biology 01/2011; 94:197-234. · 6.00 Impact Factor
