The Childhood Cancer Survivor Study: A National Cancer Institute-Supported Resource for Outcome and Intervention Research

Department of Pediatrics, The Children's Hospital of Philadelphia, Filadelfia, Pennsylvania, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 05/2009; 27(14):2308-18. DOI: 10.1200/JCO.2009.22.3339
Source: PubMed


Survival for childhood cancer has increased dramatically over the last 40 years with 5-year survival rates now approaching 80%. For many diagnostic groups, rapid increases in survival began in the 1970s with the broader introduction of multimodality approaches, often including combination chemotherapy with or without radiation therapy. With this increase in rates of survivorship has come the recognition that survivors are at risk for adverse health and quality-of-life outcomes, with risk being influenced by host-, disease-, and treatment-related factors. In 1994, the US National Cancer Institute funded the Childhood Cancer Survivor Study, a multi-institutional research initiative designed to establish a large and extensively characterized cohort of more than 14,000 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. This ongoing study, which reflects the single most comprehensive body of information ever assembled on childhood and adolescent cancer survivors, provides a dynamic framework and resource to investigate current and future questions about childhood cancer survivors.

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    • "Guided by this principle, pediatric oncologists have designed multimodality treatments, which combine surgery, chemotherapy, and craniospinal radiation [1,2]. These aggressive regimens reduce the risk of metastasis, but they are associated with disabling side effects, including neuropsychiatric challenges, stunted body growth, hormonal imbalance, epilepsy, and stroke in long-term survivors [3-5]. "
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    ABSTRACT: Leptomeningeal dissemination (LMD), the metastatic spread of tumor cells via the cerebrospinal fluid to the brain and spinal cord, is an ominous prognostic sign for patients with the pediatric brain tumor medulloblastoma. The need to reduce the risk of LMD has driven the development of aggressive treatment regimens, which cause disabling neurotoxic side effects in long-term survivors. Transposon-mediated mutagenesis studies in mice have revealed numerous candidate metastasis genes. Understanding how these genes drive LMD will require functional assessment using in vivo and cell culture models of medulloblastoma. We analyzed two genes that were sites of frequent transposon insertion and highly expressed in human medulloblastomas: Arnt (aryl hydrocarbon receptor nuclear translocator) and Gdi2 (GDP dissociation inhibitor 2). Here we show that ectopic expression of Arnt and Gdi2 promoted LMD in mice bearing Sonic hedgehog (Shh)-induced medulloblastomas. We overexpressed Arnt and Gdi2 in a human medulloblastoma cell line (DAOY) and an immortalized, nontransformed cell line derived from mouse granule neuron precursors (SHH-NPD) and quantified migration, invasiveness, and anchorage-independent growth, cell traits that are associated with metastatic competence in carcinomas. In SHH-NPD cells. Arnt and Gdi2 stimulated all three traits. In DAOY cells, Arnt had the same effects, but Gdi2 stimulated invasiveness only. These results support a mechanism whereby Arnt and Gdi2 cause cells to detach from the primary tumor mass by increasing cell motility and invasiveness. By conferring to tumor cells the ability to proliferate without surface attachment, Arnt and Gdi2 favor the formation of stable colonies of cells capable of seeding the leptomeninges. Electronic supplementary material The online version of this article (doi:10.1186/s40478-014-0085-y) contains supplementary material, which is available to authorized users.
    Full-text · Article · Jul 2014
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    • "Unnecessary radiation exposure to normal tissues, particularly in pediatric patients, is associated with increased risks of long-term adverse effects [20,21]. Lens and cochlear exposure in particular are associated with cataract formation and decreased hearing acuity respectively [22,23]. "
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    ABSTRACT: For treatment of the entire cranium using passive scattering proton therapy (PSPT) compensators are often employed in order to reduce lens and cochlear exposure. We sought to assess the advantages and consequences of utilizing compensators for the treatment of the whole brain as a component of craniospinal radiation (CSI) with PSPT. Moreover, we evaluated the potential benefits of spot scanning beam delivery in comparison to PSPT. Planning computed tomography scans for 50 consecutive CSI patients were utilized to generate passive scattering proton therapy treatment plans with and without Lucite compensators (PSW and PSWO respectively). A subset of 10 patients was randomly chosen to generate scanning beam treatment plans for comparison. All plans were generated using an Eclipse treatment planning system and were prescribed to a dose of 36Gy(RBE), delivered in 20 fractions, to the whole brain PTV. Plans were normalized to ensure equal whole brain target coverage. Dosimetric data was compiled and statistical analyses performed using a two-tailed Student's t-test with Bonferroni corrections to account for multiple comparisons. Whole brain target coverage was comparable between all methods. However, cribriform plate coverage was superior in PSWO plans in comparison to PSW (V95%; 92.9 +/- 14 vs. 97.4 +/- 5, p < 0.05). As predicted, PSWO plans had significantly higher lens exposure in comparison to PSW plans (max lens dose Gy(RBE): left; 24.8 +/- 0.8 vs. 22.2 +/- 0.7, p < 0.05, right; 25.2 +/- 0.8 vs. 22.8 +/- 0.7, p < 0.05). However, PSW plans demonstrated no significant cochlear sparing vs. PSWO (mean cochlea dose Gy(RBE): 36.4 +/- 0.2 vs. 36.7 +/- 0.1, p = NS). Moreover, dose homogeneity was inferior in PSW plans in comparison to PSWO plans as reflected by significant alterations in both whole brain and brainstem homogeneity index (HI) and inhomogeneity coefficient (IC). In comparison to both PSPT techniques, multi-field optimized intensity modulated (MFO-IMPT) spot scanning treatment plans displayed superior sparing of both lens and cochlea (max lens: 12.5 +/- 0.6 and 12.9 +/- 0.7 right and left respectively; mean cochlea 28.6 +/- 0.5 and 27.4 +/- 0.2), although heterogeneity within target volumes was comparable to PSW plans. For PSPT treatments, the addition of a compensator imparts little clinical advantage. In contrast, the incorporation of spot scanning technology as a component of CSI treatments, offers additional normal tissue sparing which is likely of clinical significance.
    Full-text · Article · Dec 2013 · Radiation Oncology
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    • "Study participants completed a baseline questionnaire beginning in 1994 and subsequent follow-up questionnaires initiated in 2003 and 2007. Additional descriptions of the CCSS methodology and participants have been published elsewhere (Leisenring et al, 2009; Robison et al, 2009). Recruitment of this study population is shown in Figure 1 and included 4569 cancer survivors X18 years of age at baseline who completed the Brief Symptom Inventory-18 (BSI-18) independently at baseline, follow-up 2 (2003–2005) and follow-up 3 (2007–2010). "
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    ABSTRACT: Background: This study investigated longitudinal patterns of psychological distress in adult survivors of childhood cancer. Methods: Participants included 4569 adult survivors in the Childhood Cancer Survivor Study Cohort (CCSS) who completed the Brief Symptom Inventory-18 on three occasions between 1994 and 2010. Longitudinal latent class analysis was used to identify discrete classes of psychological distress. Predictors of class membership were examined through logistic regression modelling with odds ratios (ORs) and 95% confidence intervals (CIs) reported. Results: Survivors were a median of 39 years of age and 30 years from diagnosis at the most recent follow-up. Most survivors reported few or no symptoms of distress over time, although subsets of survivors reported persistently elevated (depression: 8.9% anxiety: 4.8% somatisation: 7.2%) or significant increases in distress symptoms over the follow-up period (depression: 10.2% anxiety: 11.8% somatisation: 13.0%). Increasing distress symptoms were predicted by survivor perception of worsening physical health over time (depression: OR=3.3; 95% CI=2.4–4.5; anxiety: OR=3.0; 95% CI=2.2–4.0; somatisation: OR=5.3; 95% CI=3.9–7.4). Persistent distress symptoms were also predicted by survivor perception of worsening physical health over time, as well as by worsening pain and ending analgesic use. Conclusion: Subgroups of adult survivors are at-risk for chronic distress or significant increases in distress decades following their original cancer diagnosis. Routine screening of psychological distress in adult survivors of childhood cancer is warranted, especially for survivors who experience physical health morbidities.
    Full-text · Article · Jul 2013 · British Journal of Cancer
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