PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (25)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
1.  A Pilot Study of Tandem High Dose Chemotherapy with Stem Cell Rescue as Consolidation for High Risk Neuroblastoma: Children’s Oncology Group study ANBL00P1 
Bone marrow transplantation  2013;48(7):947-952.
Increasing treatment intensity has improved outcomes for children with neuroblastoma. We performed a pilot study in the Children’s Oncology Group (COG) to assess feasibility and toxicity of a tandem myeloablative regimen without total body irradiation (TBI) supported by autologous CD34 selected peripheral blood stem cells. Forty-one patients with high-risk neuroblastoma were enrolled; eight patients did not receive any myeloablative consolidation procedure, and seven received only one. Two patients out of 41 (4.9%) experienced transplant-related mortality. CD34 selection was discontinued after subjects were enrolled due to serious viral illness. From the time of study enrollment, the overall 3-year event-free survival (EFS) and overall survival (OS) were 44.8±9.6% and 59.2±9.2% (N=41). These results demonstrate that tandem transplantation in the cooperative group setting is feasible and support a randomized comparison of single versus tandem myeloablative consolidation with PBSC support for high-risk neuroblastoma.
doi:10.1038/bmt.2012.276
PMCID: PMC3638062  PMID: 23334272
pediatric; neuroblastoma; tandem transplant; hematopoietic stem cell transplant
2.  Partnership for Health-2, A Web-Based Versus Print Smoking Cessation Intervention for Childhood and Young Adult Cancer Survivors: Randomized Comparative Effectiveness Study 
Background
Smoking among cancer survivors increases the risk of late effects and second cancers. This article reports on Partnership for Health-2 (PFH-2)—an effort to develop an effective and scalable version of Partnership for Health (PFH), which was a previously tested peer-delivered telephone counseling program that doubled smoking cessation rates among childhood cancer survivors who smoke.
Objective
This paper presents results from a randomized controlled trial evaluating the effectiveness of PFH-2 in targeted and tailored Web-based versus print formats. The overall goal was to determine whether the intervention outcomes in these self-guided scalable formats approximate what was found in a more intensive telephone counseling program.
Methods
This study was a randomized controlled trial with a 15-month follow-up that included 374 smokers who were survivors of childhood or young adult cancers, recruited from five survivorship clinics. Participants were randomly assigned to a Web-based or print format of the PFH intervention; all had access to free pharmacotherapy. The website was designed to provide new content at each log-on, and a peer counselor moderated a forum/chat feature. The primary outcome was smoking status at 15 months post randomization.
Results
In total, 58.3% (77/132) of Web participants logged on at least once (mean visits 3.25). Using multiple imputation methods for missing data, there were similar rates of cessation in the two arms (print: 20/128, 15.6%; Web: 33/201, 6.4%), and no differences in quit attempts or readiness to quit. The quit rates were equivalent to those found in our previous telephone counseling intervention. There were high rates of satisfaction with both of the PFH-2 interventions.
Conclusions
The print and Web formats yielded equivalent levels of success to those found with our telephone-delivered intervention and are comparable to other Internet treatment studies. This study provides important options for survivorship programs that may not have resources for interpersonal forms of cessation counseling. Efforts to increase patient use of the interventions may result in higher cessation rates.
Trial Registration
Clinicaltrials.gov NCT00588107; http://clinicaltrials.gov/ct2/show/NCT00588107 (Archived by WebCite at http://www.webcitation.org/6K1gJtFEC).
doi:10.2196/jmir.2533
PMCID: PMC3841363  PMID: 24195867
cancer survivors; smoking cessation; cancer prevention
3.  Risk Factors Associated with Secondary Sarcomas in Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study 
Purpose
Childhood cancer survivors have an increased risk of secondary sarcomas. To better identify those at risk, the relationship between therapeutic dose of chemotherapy and radiation and secondary sarcoma should be quantified.
Methods and Materials
We conducted a nested case-control study of secondary sarcomas (105 cases, 422 matched controls) in a cohort of 14,372 childhood cancer survivors. Radiation dose at the second malignant neoplasm (SMN) site and use of chemotherapy were estimated from detailed review of medical records. Odds ratios (ORs) and 95% confidence intervals were estimated by conditional logistic regression. Excess odds ratio (EOR) was modeled as a function of radiation dose, chemotherapy, and host factors.
Results
Sarcomas occurred a median of 11.8 years (range: 5.3-31.3 years) from original diagnosis. Any exposure to radiation was associated with increased risk of subsequent sarcoma (OR = 4.1, 95% CI = 1.8-9.5). A dose-response relation was observed, with elevated risks at doses between 10 - 29.9 Gy (OR = 15.6, 95% CI = 4.5-53.9), 30 - 49.9 Gy (OR = 16.0, 95% CI 3.8-67.8) and >50 Gy (OR = 114.1, 95% CI 13.5-964.8). Anthracycline exposure was associated with sarcoma risk (OR = 3.5, 95% CI = 1.6-7.7) adjusting for radiation dose, other chemotherapy, and primary cancer. Adjusting for treatment, survivors with a first diagnosis of Hodgkin lymphoma (HL; OR=10.7, 95% CI = 3.1-37.4) or primary sarcoma (OR=8.4, 95% CI = 3.2-22.3) were more likely to develop a sarcoma.
Conclusions
Of the risk factors evaluated, radiation exposure was the most important for secondary sarcoma development in childhood cancer survivors; anthracycline chemotherapy exposure was also associated with increased risk.
doi:10.1016/j.ijrobp.2011.11.022
PMCID: PMC3423483  PMID: 22795729
Childhood cancer survivors; secondary sarcomas; radiation late effects
4.  SECONDARY GASTROINTESTINAL MALIGNANCIES IN CHILDHOOD CANCER SURVIVORS: A COHORT STUDY 
Annals of internal medicine  2012;156(11):757-260.
Background
Childhood cancer survivors develop gastrointestinal malignancies more frequently and at a younger age than the general population, but risk factors for their development have not been well characterized.
Objective
To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMN) in childhood cancer survivors.
Design
Retrospective cohort study.
Setting
The Childhood Cancer Survivor Study, a multi-center study of childhood cancer survivors diagnosed between 1970 and 1986.
Patients
14,358 survivors of a malignancy diagnosed at < 21 years who had survived for 5 or more years from initial diagnosis.
Measurements
Standardized incidence ratios (SIR) for gastrointestinal SMN were calculated using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development.
Results
At median follow-up of 22.8 years (range: 5.5-30.2), 45 gastrointestinal malignancies were identified. Gastrointestinal SMN risk was 4.6-fold higher in childhood cancer survivors than the general population (95% confidence interval [CI]: 3.5-6.1). Colorectal cancer SIR was 4.2 (95% CI: 2.8-6.3). The highest gastrointestinal SMN risk was associated with abdominal radiation (SIR=11.2, 95% CI: 7.6-16.4). However, survivors not exposed to radiation had a significantly increased risk (SIR=2.4, 95% CI-1.4-3.9). In addition to abdominal radiation, high dose procarbazine (RR=3.2, 95% CI 1.1-9.4) and platinum drugs (RR 7.6, 95% CI: 2.3-25.5) independently increased the gastrointestinal SMN risk.
Limitations
This cohort has not yet attained an age at which gastrointestinal malignancy risk is greatest.
Conclusions
Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMN. These findings suggest that surveillance of at-risk childhood cancer survivors should commence at a younger age than recommended for the general population.
doi:10.1059/0003-4819-156-11-201206050-00002
PMCID: PMC3554254  PMID: 22665813
5.  How confident are young adult cancer survivors in managing their survivorship care? A report from the LIVESTRONG™ Survivorship Center of Excellence Network 
Introduction
This study examined the association between sociodemographic, cancer treatment, and care delivery factors on young adult cancer survivors’ confidence in managing their survivorship care.
Methods
Survivors aged 18-39 years (n=376) recruited from the LIVESTRONG™ Survivorship Center of Excellence Network sites completed a survey assessing self-reported receipt of survivorship care planning, expectations of their providers, and confidence in managing their survivorship care. Multivariate logistic regression identified characteristics of those reporting low confidence in managing their survivorship care.
Results
Mean age was 28 years; mean interval from diagnosis was 9 ± 8 years. Seventy-one percent reported currently attending an oncology survivorship clinic. Regarding survivorship care planning, 33% did not have copies of their cancer-related medical records, 48% did not have a treatment summary, and 55% had not received a survivorship care plan. Seventy percent identified the oncologist as the most important health care provider for decisions regarding test and treatment decisions, while 10% reported using a “shared-care model” involving both primary care providers and oncologists. Forty-one percent were classified as having low confidence in managing survivorship care. In multivariate analysis, low confidence was associated with non-white ethnicity and lack of a survivorship care plan (both p<.05).
Discussion/Conclusion
Findings suggest that provision of survivorship care plans for young adult cancer survivors can be used to improve confidence in managing survivorship care, particularly for ethnic minorities.
Implications for Cancer Survivors
Survivors should consider advocating for receipt of a survivorship care plan as it may facilitate confidence as a consumer of survivorship care.
doi:10.1007/s11764-011-0199-1
PMCID: PMC3229469  PMID: 22042661
neoplasm; young adult; cancer survivors; delivery of health care; survivorship care plan
6.  Survivors of Childhood Cancer Have Increased Risk for Gastrointestinal Complications Later in Life 
Gastroenterology  2011;140(5):1464-1471.e1.
Background & Aims
Children who receive cancer therapy experience numerous acute gastrointestinal (GI) toxicities. However, the long-term GI consequences have not been extensively studied. We evaluated the incidence of adverse long-term GI outcomes and identified treatment-related risk factors.
Methods
Upper GI, hepatic, and lower GI adverse outcomes were assessed in cases randomly selected from participants in the Childhood Cancer Survivor Study, a study of 14,358 survivors of childhood cancer who were diagnosed between 1970 and 1986; data were compared with those from siblings. The median age at cancer diagnosis was 6.8 years (0–21.0 years), the median age at outcome assessment was 23.2 years (5.6–48.9 years) for survivors and 26.6 years (1.8–56.2 years) for siblings. Rates of self-reported, late complications of the GI tract (occurred 5 or more years after cancer diagnosis) were determined and associated with patient characteristics and cancer treatments, adjusting for age, sex, and race; data were compared with those from siblings.
Results
Compared with siblings, survivors had increased risk for late-onset complications of the upper GI tract (relative risk [RR]=1.8; 95% confidence interval [CI], 1.6–2.0), liver (RR=2.1; 95% CI, 1.8–2.5), and lower GI tract (RR=1.9; 1.7–2.2). The RR for requiring colostomy, ileostomy, or liver biopsy, or for developing liver cirrhosis were 5.6 (95% CI, 2.4–13.1), 24.1 (95% CI, 7.5–77.8), and 8.9 (95% CI, 2.0–40.0), respectively. Older age at diagnosis, intensified therapy, abdominal radiation, and abdominal surgery increased the risk of certain GI complications.
Conclusions
Individuals who received therapy for cancer during childhood have an increased risk of developing GI complications later in life.
doi:10.1053/j.gastro.2011.01.049
PMCID: PMC3081911  PMID: 21315721
tumor; chemotherapy; side effect; toxicity; pediatric
7.  Inconsistent mammography perceptions and practices among women at risk of breast cancer following a pediatric malignancy: a report from the Childhood Cancer Survivor Study 
Cancer causes & control : CCC  2010;21(10):1585-1595.
Women treated with chest radiation for a pediatric cancer have low mammography screening rates despite their high risk for breast cancer. This study characterized the relationship between perceptions of mammography and screening practices. A cross-sectional survey was administered to 523 women in North America who were treated with chest radiation before 21 years of age. Women with inconsistent mammography perceptions and practices were identified using the Pros and Cons of Mammography for perceptions and Transtheoretical Model stages of adoption for prior and intended screening practices. Classification and regression tree (CART) analysis was used to identify barriers to and facilitators of screening among women with positive and negative perceptions. Nearly one-third of the cohort had inconsistent perceptions and practices: 37.4% had positive perceptions and were not having mammograms; 27.6% had negative/neutral perceptions and were having mammograms. Regardless of perceptions, a recent physician’s recommendation for mammography, age ≥ 40, and interest in routine health care were universally associated with mammography practices. For women with positive perceptions and a physician’s recommendation, barriers to screening included high acceptance coping, low active-planning coping, and high internal health locus of control. For women with negative perceptions, acknowledging the importance of asymptomatic screening was associated with mammography.
doi:10.1007/s10552-010-9587-5
PMCID: PMC2941535  PMID: 20506037
Cancer survivorship; Late effects; Screening; Transtheoretical model; Stages of adoption
8.  Phase I Study of Decitabine with Doxorubicin and Cyclophosphamide in Children with Neuroblastoma and Other Solid Tumors: A Children’s Oncology Group Study 
Pediatric blood & cancer  2010;55(4):629-638.
Background
Demethylating agents may alter the expression of genes involved in chemotherapy resistance. We conducted a phase I trial to determine the toxicity and molecular effects of the demethylating agent, decitabine, followed by doxorubicin and cyclophosphamide in children with refractory solid tumors.
Procedure
Stratum A included children with any solid tumor; Stratum B included neuroblastoma patients only. Patients received a 1-hour decitabine infusion for 7 days, followed by doxorubicin (45mg/m2) and cyclophosphamide (1g/m2) on day 7. Pharmacokinetic studies were performed after the first dose of decitabine. Biological studies included methylation and gene expression analyses of caspase-8, MAGE-1 and fetal hemoglobin (HbF), and expression profiling of pre- and post-treatment peripheral blood and bone marrow cells.
Results
The maximum-tolerated dose of decitabine was 5 mg/m2/d for 7 days. Dose-limiting toxicities at 10 mg/m2/d were neutropenia and thrombocytopenia. Decitabine exhibited rapid clearance from plasma. Three of 9 patients in Stratum A and 4/12 patients in Stratum B had stable disease for ≥4 months. Sustained MAGE-1 demethylation and increased HbF expression were observed in the majority of patients post-treatment (12/20 and 14/16 respectively). Caspase-8 promoter demethylation and gene expression were seen in 2/7 bone marrow samples. Differentially expressed genes were identified by microarray analysis.
Conclusion
Low-dose decitabine when combined with doxorubicin/cyclophosphamide has tolerable toxicity in children. However, doses of decitabine capable of producing clinically relevant biologic effects were not well tolerated with this combination. Alternative strategies of combining demethylating agents with non-cytotoxic, biologically targeted agents such as histone deactelyase inhibitors should be explored.
doi:10.1002/pbc.22607
PMCID: PMC3025700  PMID: 20589651
demethylation; decitabine; pediatric solid tumor; neuroblastoma
9.  Phase II Randomized Comparison of Topotecan Plus Cyclophosphamide Versus Topotecan Alone in Children With Recurrent or Refractory Neuroblastoma: A Children's Oncology Group Study 
Journal of Clinical Oncology  2010;28(24):3808-3815.
Purpose
Single-agent topotecan (TOPO) and combination topotecan and cyclophosphamide (TOPO/CTX) were compared in a phase II randomized trial in relapsed/refractory neuroblastoma. Because responders often underwent further therapies, novel statistical methods were required to compare the long-term outcome of the two treatments.
Patients and Methods
Children with refractory/recurrent neuroblastoma (only one prior aggressive chemotherapy regimen) were randomly assigned to daily 5-day topotecan (2 mg/m2) or combination topotecan (0.75 mg/m2) and cyclophosphamide (250 mg/m2). A randomized two-stage group sequential design enrolled 119 eligible patients. Toxicity and response were estimated. Long-term outcome of protocol therapy was assessed using novel methods—causal inference—which allowed adjustment for the confounding effect of off-study therapies.
Results
Seven more responses were observed for TOPO/CTX (complete response [CR] plus partial response [PR], 18 [32%] of 57) than TOPO (CR+PR, 11 [19%] of 59;P = .081); toxicity was similar. At 3 years, progression-free survival (PFS) and overall survival (OS) were 4% ± 2% and 15% ± 4%, respectively. PFS was significantly better for TOPO/CTX (P = .029); there was no difference in OS. Older age at diagnosis and lack of MYCN amplification predicted increased OS (P < .05). Adjusting for randomized treatment effect and subsequent autologous stem-cell transplantation, there was no difference between TOPO and TOPO/CTX in terms of the proportion alive at 2 years.
Conclusion
TOPO/CTX was superior to TOPO in terms of PFS, but there was no OS difference. After adjustment for subsequent therapies, no difference was detected in the proportion alive at 2 years. Causal inference methods for assessing long-term outcomes of phase II therapies after subsequent treatment can elucidate effects of initial therapies.
doi:10.1200/JCO.2009.27.5016
PMCID: PMC2940398  PMID: 20660830
10.  Disseminating a smoking cessation intervention to childhood and young adult cancer survivors: baseline characteristics and study design of the partnership for health-2 study 
BMC Cancer  2011;11:165.
Background
Partnership for Health-2 (PFH-2) is a web-based version of Partnership for Health, an evidence-based smoking cessation intervention for childhood cancer survivors. This paper describes the PFH-2 intervention and baseline data collection.
Methods
374 childhood and young adult cancer survivors were recruited from five cancer centers and participated in the baseline assessment. At baseline, participants completed measures of their smoking behavior, self-efficacy and stage of change for quitting smoking as well as psychological and environmental factors that could impact their smoking behavior.
Results
At baseline, 93% of survivors smoked in the past seven days; however, 89% smoked a pack or less during this period. Forty-seven percent were nicotine dependent, and 55% had made at least one quit attempt in the previous year. Twenty-two percent of survivors were in contemplation for quitting smoking; of those 45% were somewhat or very confident that they could quit within six months. Sixty-three percent were in preparation for quitting smoking; however, they had relatively low levels of confidence that they could quit smoking in the next month. In multivariate analyses, stage of change, self-efficacy, social support for smoking cessation, smoking policy at work and home, fear of cancer recurrence, perceived vulnerability, depression, BMI, and contact with the healthcare system were associated with survivors' smoking behavior.
Discussions/Conclusions
A large proportion of the sample was nicotine dependent, yet motivated to quit. Individual- interpersonal- and environmental-level factors were associated with survivors' smoking behavior. Smoking is particularly dangerous for childhood and young adult cancer survivors. This population may benefit from a smoking cessation intervention designed to build self-efficacy and address other known predictors of smoking behavior.
doi:10.1186/1471-2407-11-165
PMCID: PMC3114793  PMID: 21569345
11.  A Model-Based Estimate of Cumulative Excess Mortality in Survivors of Childhood Cancer 
Annals of internal medicine  2010;152(7):409-W138.
Background
Although childhood cancer survival rates have dramatically increased, survivors continue to face elevated risks for life-threatening late-effects, including secondary cancers.
Objective
We sought to estimate the cumulative impact of disease- and treatment-related mortality risks on survivor life expectancy.
Design
State-transition model.
Setting
To simulate the lifetime clinical course of childhood cancer survivors, we estimated probabilities for the following competing risks from published studies: (1) risk of dying from original cancer diagnosis; (2) excess mortality from non-recurrence late-effects; and (3) background mortality.
Patients
Five-year childhood cancer survivors.
Measurements
Lifetime cause-specific mortality, life expectancy, cause-specific attributable proportion of overall mortality risk, conditional ten-year mortality probabilities.
Results
For a cohort of 15-year-old five-year survivors, diagnosed with cancer at age 10, the average lifetime probability of mortality was 0.10 for late-recurrence, 0.15 for treatment-related subsequent cancers, cardiac, pulmonary, and external causes, and 0.05 for other excess risk. Life expectancy for the cohort of 15-year-olds was 50.6 years, a loss of 10.4 years (17.1%) compared to the general population. Reduction in life expectancy varied by diagnosis, ranging from 4.0 years (6.0%) for kidney tumors to more than 17.8 years (>28.2%) for brain and bone tumor survivors, and was sensitive to late-recurrence mortality risk and duration of excess mortality risks.
Limitations
Estimates are based on data for survivors treated 20–40 years ago; patients treated more recently may have more favorable outcomes.
Conclusions
Despite surviving their initial cancer, childhood cancer survivors face considerable mortality during adulthood, with excess risks reducing life expectancy by as much as 28%. Our findings underscore the need to monitor the health of current survivors and carefully evaluate therapies with known late toxicities in newly diagnosed patients.
doi:10.1059/0003-4819-152-7-201004060-00005
PMCID: PMC3086591  PMID: 20368646
12.  Physician Preferences and Knowledge Gaps Regarding the Care of Childhood Cancer Survivors: A Mailed Survey of Pediatric Oncologists 
Journal of Clinical Oncology  2009;28(5):878-883.
Purpose
Little is known about physicians' attitudes and knowledge regarding the health care needs of childhood cancer survivors (CCS). We sought to obtain pediatric cancer physicians' self-reported attitudes and knowledge regarding this population.
Methods
A mailed survey was sent to 1,159 pediatric oncologists in the United States.
Results
A total of 655 surveys were returned (ie, 57% response rate). Median age of respondents was 47 years (range, 31 to 82 years); 57% were men. Respondents practiced for a median 14 years (range, 1 to 50 years) and reported seeing a median of 21 patients per week (range, 0 to 250 patients per week). When comfort levels in caring for CCS were described (ie, 1 = very uncomfortable; 7 = very comfortable), respondents were most comfortable with survivors ≤ 21 years (mean ± standard deviation, 6.2 ± 1.3 level), were less comfortable (5.0 ± 1.5 level) with those older than 21 years but less than 30 years old, and were uncomfortable with CCS ≥ 30 years (2.9 ± 1.7 level). In response to a clinical vignette of a 29-year-old woman treated with mantle radiation for Hodgkin's lymphoma at 16 years of age, and on the basis of available guidelines, 34% of respondents did not appropriately recommend yearly breast cancer surveillance; 43% of respondents did not appropriately recommend cardiac surveillance; and 24% of respondents did not appropriately recommend yearly thyroid surveillance. Those with greater self-reported familiarity with available long-term follow-up (LTFU) guidelines (odds ratio [OR], 1.33; 95% CI, 1.15 to 1.54) and with receipt of training in the care of CCS (OR, 1.73; 95% CI, 1.18 to 2.52) were more likely to have answered all three questions correctly.
Conclusion
Pediatric oncologists express a range of preferences with regard to LTFU of CCS. Many appear unfamiliar with LTFU surveillance guidelines.
doi:10.1200/JCO.2009.25.6107
PMCID: PMC3040043  PMID: 20038717
13.  Suicide Ideation in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2009;28(4):655-661.
Purpose
To evaluate risk of suicide ideation (SI) after childhood cancer, prevalence of SI in a cohort of adult survivors of pediatric cancers was compared with prevalence in a sibling comparison group. The relationship of SI to cancer treatment and current health was examined, and the hypothesis that poor physical health is significantly associated with suicidality, after adjusting for depression, was specifically tested.
Methods
Nine thousand one hundred twenty-six adult survivors of childhood cancer and 2,968 siblings enrolled onto the Childhood Cancer Survivor Study completed a survey describing their demographics and medical and psychological functioning, including SI in the prior week.
Results
Of survivors, 7.8% reported SI compared with 4.6% of controls (odds ratio = 1.79; 95% CI, 1.4 to 2.4). Suicidality was unrelated to age, age at diagnosis, sex, cancer therapy, recurrence, time since diagnosis, or second malignancy. SI was associated with primary CNS cancer diagnosis, depression, and poor health outcomes including chronic conditions, pain, and poor global health rating. A logistic regression analysis showed that poor current physical health was significantly associated with SI even after adjusting for cancer diagnosis and depression.
Conclusion
Adult survivors of childhood cancers are at increased risk for SI. Risk of SI is related to cancer diagnosis and post-treatment mental and physical health, even many years after completion of therapy. The association of suicidal symptoms with physical health problems is important because these may be treatable conditions for which survivors seek follow-up care and underscores the need for a multidisciplinary approach to survivor care.
doi:10.1200/JCO.2009.22.8635
PMCID: PMC2816000  PMID: 19841325
14.  General Internist Communication about Sexual Function with Cancer Survivors 
Journal of General Internal Medicine  2009;24(Suppl 2):407-411.
ABSTRACT
BACKGROUND
Sexual dysfunction is an important issue that affects many cancer survivors who are increasingly being cared for by internists.
OBJECTIVE
To examine the attitudes and reported practices of internists regarding survivorship care as it pertains to sexual dysfunction.
DESIGN
Surveys were sent to 406 physicians affiliated with the Department of Internal Medicine at the University of Colorado Denver School of Medicine. Of the 319 eligibles, 227 were returned (71% RR).
MAIN RESULTS
Of the 227 responders, 46% were “somewhat/very” likely to initiate a conversation about sexual dysfunction; 62% “never/rarely” addressed sexual dysfunction. Each additional weekly hour spent in patient care was associated with a 2% increase in the likelihood of sexual dysfunction being addressed or discussions about sexual dysfunction being initiated. Reported inadequate preparation/formal training around survivorship issues was associated with sexual dysfunction being addressed less often (odds ratio [OR] = 0.45). Perception of patient anxiety or fears about health was associated with sexual dysfunction being addressed more often (OR = 2.38). Perceived preparedness to evaluate long-term effects was associated with a greater likelihood of physicians initiating discussions about sexual functioning (OR = 2.49).
CONCLUSIONS
Cancer survivors receive their long-term care from internists. Our results suggest that sexual dysfunction is often not addressed during their follow-up care. Additional training is needed to prepare physicians to negotiate this difficult issue.
doi:10.1007/s11606-009-1026-5
PMCID: PMC2763155  PMID: 19838840
general internist; survivorship; sexuality communication
15.  Radiation Dose and Breast Cancer Risk in the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2009;27(24):3901-3907.
Purpose
The purpose of this study was to quantify the risk of breast cancer in relation to radiation dose and chemotherapy among survivors of childhood cancer.
Methods
We conducted a case-control study of breast cancer in a cohort of 6,647 women who were 5-year survivors of childhood cancer and who were treated during 1970 through 1986. One hundred twenty patients with histologically confirmed breast cancer were identified and were individually matched to four selected controls on age at initial cancer and time since initial cancer. Medical physicists estimated radiation dose to the breast tumor site and ovaries on the basis of medical records.
Results
The odds ratio for breast cancer increased linearly with radiation dose, and it reached 11-fold for local breast doses of approximately 40 Gy relative to no radiation (P for trend < .0001). Risk associated with breast irradiation was sharply reduced among women who received 5 Gy or more to the ovaries (P = .002). The excess odds ratio per Gy was 0.36 for those who received ovarian doses less than 5 Gy and was 0.06 for those who received higher doses. Radiation-related risk did not vary significantly by age at exposure. Borderline significantly elevated risks were seen for doxorubicin, dactinomycin, dacarbazine, and carmustine.
Conclusion
Results confirm the radiation sensitivity of the breast in girls age 10 to 20 years but do not demonstrate a strong effect of age at exposure within this range. Irradiation of the ovaries at doses greater than 5 Gy seems to lessen the carcinogenic effects of breast irradiation, most likely by reducing exposure of radiation-damaged breast cells to stimulating effects of ovarian hormones.
doi:10.1200/JCO.2008.20.7738
PMCID: PMC2734395  PMID: 19620485
16.  Long-term Outcomes in Survivors of Neuroblastoma: A Report From the Childhood Cancer Survivor Study 
Background
The 5-year survival rate for individuals with neuroblastoma is approaching 70%. Few data exist, however, on the long-term outcomes of these patients, who are often treated at a very young age.
Methods
Outcome data were obtained for 954 5-year neuroblastoma survivors who were diagnosed in 1970–1986 and enrolled in the Childhood Cancer Survivor Study (CCSS). Late mortality, second malignant neoplasms, and chronic health conditions were analyzed in relation to treatment factors using Poisson regression models and their modification with generalized estimating equations. Neuroblastoma survivors were compared with a cohort of 3899 siblings of CCSS participants for risk of chronic health conditions and selected sociodemographic outcomes. All statistical tests were two-sided.
Results
Six percent of patients died more than 5 years after their diagnosis (standardized mortality ratio = 5.6; 95% confidence interval [CI] = 4.4 to 6.9). The most common causes of death were disease recurrence (n = 43) and second malignant neoplasms (n = 13). The cumulative incidence of second malignant neoplasms was 3.5% at 25 years and 7.0% at 30 years after diagnosis. Compared with the sibling cohort, survivors had an increased risk of selected chronic health conditions (risk ratio [RR] = 8.3; 95% CI = 7.1 to 9.7) with a 20-year cumulative incidence of 41.1%. The most prevalent outcomes involved the neurological, sensory, endocrine, and musculoskeletal systems, with 20-year cumulative incidences of 29.8%, 8.6%, 8.3%, and 7.8%, respectively. Neuroblastoma survivors who were treated with multimodality therapy were more likely to develop a chronic health condition than survivors treated with surgery alone (RR = 2.2; 95% CI = 1.6 to 3.0). Neuroblastoma survivors were less likely than siblings to have ever been employed (P = .04) or to be married (P < .001) and had a lower personal income (P = .009).
Conclusions
Neuroblastoma survivors have an increased rate of mortality and second malignant neoplasms, relative to the age- and sex-comparable US population, and of chronic health conditions, relative to their siblings, which underscores the need for long-term medical surveillance.
doi:10.1093/jnci/djp230
PMCID: PMC2728747  PMID: 19648511
18.  Surveillance for Breast Cancer in Women Treated with Chest Radiation for a Childhood, Adolescent or Young Adult Cancer: A Report from the Children's Oncology Group 
Annals of internal medicine  2010;152(7):444-W154.
Background
Women treated with therapeutic chest radiation may develop breast cancer.
Purpose
Summarize breast cancer risk and breast cancer surveillance in women following chest radiation for a pediatric or young adult cancer.
Data Sources
Studies from MEDLINE, EMBASE, Cochrane Library, and CINAHL (1966 through December 2008).
Study Selection
Articles selected to answer any of 3 questions: 1) What is the incidence and excess risk of breast cancer in women following chest radiation for a pediatric or young adult cancer? 2) For these women, are the clinical characteristics of the breast cancer and the outcomes following therapy different than for women with sporadic breast cancer in the general population? 3) What are the potential benefits and harms associated with breast cancer surveillance among women exposed to chest radiation?
Data Extraction
Three investigators independently extracted data and assessed study quality.
Data Synthesis
Standardized incidence ratios ranged from 13.3 to 55.5; cumulative incidence of breast cancer by 40–45 years of age ranged from 13–20%. Risk of breast cancer increased linearly with chest radiation dose. Available limited evidence suggests that the characteristics of the breast cancers in these women and the outcomes following diagnosis are similar to those in the general population; these breast cancers can be detected by mammography, though sensitivity is limited.
Limitations
Limitations include study heterogeneity, design and small sample size.
Conclusions
Women treated with chest radiation have a substantially elevated risk of breast cancer at a young age, which does not appear to plateau. Among this high risk population, there appears to be a benefit associated with early detection. Further research is required to better define the harms and benefits of lifelong surveillance.
doi:10.1059/0003-4819-152-7-201004060-00009
PMCID: PMC2857928  PMID: 20368650
19.  Clinical Cancer Advances 2008: Major Research Advances in Cancer Treatment, Prevention, and Screening—A Report From the American Society of Clinical Oncology 
Journal of Clinical Oncology  2008;27(5):812-826.
A MESSAGE FROM ASCO'S PRESIDENT
Nearly 40 years ago, President Richard Nixon signed the National Cancer Act, mobilizing the country's resources to make the “conquest of cancer a national crusade.” That declaration led to a major investment in cancer research that has significantly improved cancer prevention, treatment, and survival. As a result, two thirds of people diagnosed with cancer today will live at least 5 years after diagnosis, compared with just half in the 1970s. In addition, there are now more than 12 million cancer survivors in the United States—up from 3 million in 1971.
Scientifically, we have never been in a better position to advance cancer treatment. Basic scientific research, fueled in recent years by the tools of molecular biology, has generated unprecedented knowledge of cancer development. We now understand many of the cellular pathways that can lead to cancer. We have learned how to develop drugs that block those pathways; increasingly, we know how to personalize therapy to the unique genetics of the tumor and the patient.
Yet in 2008, 1.4 million people in the United States will still be diagnosed with cancer, and more than half a million will die as a result of the disease. Some cancers remain stubbornly resistant to treatment, whereas others cannot be detected until they are in their advanced, less curable stages. Biologically, the cancer cell is notoriously wily; each time we throw an obstacle in its path, it finds an alternate route that must then be blocked.
To translate our growing basic science knowledge into better treatments for patients, a new national commitment to cancer research is urgently needed. However, funding for cancer research has stagnated. The budgets of the National Institutes of Health and the National Cancer Institute have failed to keep pace with inflation, declining up to 13% in real terms since 2004. Tighter budgets reduce incentives to support high-risk research that could have the largest payoffs. The most significant clinical research is conducted increasingly overseas. In addition, talented young physicians in the United States, seeing less opportunity in the field of oncology, are choosing other specialties instead.
Although greater investment in research is critical, the need for new therapies is only part of the challenge. Far too many people in the United States lack access to the treatments that already exist, leading to unnecessary suffering and death. Uninsured cancer patients are significantly more likely to die than those with insurance, racial disparities in cancer incidence and mortality remain stark, and even insured patients struggle to keep up with the rapidly rising cost of cancer therapies.
As this annual American Society of Clinical Oncology report of the major cancer research advances during the last year demonstrates, we are making important progress against cancer. But sound public policies are essential to accelerate that progress. In 2009, we have an opportunity to reinvest in cancer research, and to support policies that will help ensure that every individual in the United States receives potentially life-saving cancer prevention, early detection, and treatment.
Sincerely, Richard L. Schilsky, MD President American Society of Clinical Oncology
doi:10.1200/JCO.2008.21.2134
PMCID: PMC2645086  PMID: 19103723
20.  Long-Term Smoking Cessation Outcomes Among Childhood Cancer Survivors in the Partnership for Health Study 
Journal of Clinical Oncology  2009;27(1):52-60.
Purpose
Partnership for Health (PFH) was found to increase smoking cessation among smokers in the Childhood Cancer Survivors Study (CCSS) at the 8- and 12-month postbaseline follow-up. This report provides outcomes at 2 to 6 years postbaseline; the primary outcome is a four-category smoking status variable (quit at all follow-ups, quit at final follow-up only, smoker at all follow-ups, and smoker at final follow-up only); quit attempts among those who reported smoking at the final follow-up is a secondary outcome.
Methods
PFH was a randomized control trial with two conditions, peer phone counseling (PC) and self-help (SH), that involved smokers (n = 796) enrolled in the CCSS cohort.
Results
Long-term quit rates were higher in PC versus SH participants. Long-term smoking cessation outcomes were lower among those who were nicotine dependent, of lower educational levels, and among men, and were higher among those who used nicotine replacement therapy and who had higher levels of situational self-efficacy. There were no significant differences in relapse rates between conditions or in quit attempts among continued smokers.
Conclusion
Cessation rates continue to be significantly higher among participants in the PC condition versus SH, although the differences were not large. This article highlights differences in long-term engagement with smoking cessation among those who received the intervention.
doi:10.1200/JCO.2007.13.0880
PMCID: PMC2645097  PMID: 19047296
21.  Lung Metastases in Neuroblastoma at Initial Diagnosis: A Report from the International Neuroblastoma Risk Group (INRG) Project 
Pediatric blood & cancer  2008;51(5):589-592.
Background
Neuroblastoma is the most common extracranial pediatric solid cancer. Lung metastasis is rarely detected in children with newly diagnosed neuroblastoma. We aimed to describe the incidence, clinical characteristics, and outcome of patients with lung metastasis at initial diagnosis using a large international database.
Procedure
The subset of patients from the International Neuroblastoma Risk Group database with INSS stage 4 neuroblastoma and known data regarding lung metastasis at diagnosis was selected for analysis. Clinical and biological characteristics were compared between patients with and without lung metastasis. Survival for patients with and without lung metastasis was estimated by Kaplan-Meier methods. Cox proportional hazards methods were used to determine the independent prognostic value of lung metastasis at diagnosis.
Results
Of the 2,808 patients with INSS stage 4 neuroblastoma diagnosed between 1990 and 2002, 100 patients (3.6%) were reported to have lung metastasis at diagnosis. Lung metastasis was more common among patients with MYCN amplified tumors, adrenal primary tumors, or elevated lactate dehydrogenase (LDH) levels (p < 0.02 in each case). Five-year overall survival ± standard error for patients with lung metastasis was 34.5% ± 6.8% compared to 44.7% ± 1.3% for patients without lung metastasis (p=0.0002). However, in multivariable analysis, the presence of lung metastasis was not independently predictive of outcome.
Conclusions
Lung metastasis at initial diagnosis of neuroblastoma is associated with MYCN amplification and elevated LDH levels. Although lung metastasis at diagnosis was not independently predictive of outcome in this analysis, it remains a useful prognostic marker of unfavorable outcome.
doi:10.1002/pbc.21684
PMCID: PMC2746936  PMID: 18649370
Neuroblastoma; Lung Metastases; Pulmonary; MYCN
22.  Cancer Care and Cancer Survivorship Care in the United States: Will We Be Able to Care for These Patients in the Future? 
Journal of Oncology Practice  2009;5(3):119-123.
The combination of a shortfall in oncologists and primary care physicians and an increased number of patients using more health care resources raises concerns about our health care system's ability to accommodate future patients with cancer and cancer survivors.
Studies have predicted a shortfall in the workforces of oncologists and primary care physicians in the coming years. These estimates are based on the number of current physicians, those leaving the profession, and the rate of new physicians joining each profession, as benchmarked against the number of patients needing care. For active cancer treatment, and particularly for the care of cancer survivors, it is likely that current calculations underestimate the shortfalls which will occur in the next 5 to 10 years. Ever more complex cancer therapies are leading to better outcomes with improved cure rates and prolonged survivals even for patients who ultimately succumb to their disease, resulting in a substantial increase in utilization of health care resources. Due to these factors, utilization of health care resources by cancer patients and cancer survivors is climbing at a rate greater than would be predicted by patient numbers alone. The combination of an increased number of patients utilizing more resources calls into question the ability of our healthcare system to meet the needs of cancer patients and cancer survivors in the future. It is crucial that innovative models of care (utilizing nonphysician providers) be developed and evaluated to assure quality care and services for this growing population.
doi:10.1200/JOP.0932001
PMCID: PMC2790692  PMID: 20856750
23.  Breast Cancer Surveillance Practices Among Women Previously Treated With Chest Radiation for a Childhood Cancer 
Context
Women treated with chest radiation for a pediatric malignancy have a significantly increased risk of breast cancer at a young age and are recommended to have an annual screening mammogram starting at age 25 or 8 years after radiation, whichever occurs last.
Objective
Characterize the breast cancer surveillance practices among female pediatric cancer survivors who were treated with chest radiation and identify correlates of screening.
Design, Setting, Participants
Between June 2005 and August 2006, a 114-item questionnaire was administered to a random sample of 625 female pediatric cancer survivors who had been treated with chest radiation and were age 25–50 and participating in the Childhood Cancer Survivor Study (CCSS), a North American cohort of long-term survivors diagnosed from 1970–1986. Comparisons were made with similarly aged pediatric cancer survivors not treated with chest radiation (N=639) and the CCSS siblings cohort (N=712).
Main Outcome Measure
Screening mammogram within the previous two years.
Results
Of 1976 cancer survivors and siblings who were contacted, 87.9% participated. Among the 551 women with a history of chest radiation, 55% reported a screening mammogram in the past two years (ages 25–39, 36.5%; 95% confidence interval [CI], 31.0%–42.0%; ages 40–50, 76.5%; 95% CI, 71.3%–81.7%). In comparison, 40.5% of survivors without chest radiation and 37.0% of CCSS siblings reported a screening mammogram in the same time interval. Notably, among women with a history of chest radiation, 47.3% (95% CI, 41.6%–53.0%) of those under age 40 had never had a mammogram and only 52.6% (95% CI, 46.4%–58.8%) of women ages 40–50 were being regularly screened (two mammograms within four years). Screening rates were higher among women who reported a physician recommendation compared to those who did not (ages 25–39, 76.0% vs. 17.6%; ages 40–50, 87.3% vs. 58.3%). In multivariable models, the association was particularly strong for younger women (ages 25–39, prevalence ratio [PR] = 3.0, 95% CI, 2.0–4.0; ages 40–50, PR = 1.3, 95% CI, 1.1–1.6).
Conclusions
In this study cohort of women who had childhood cancer treated with chest radiation, 63.5% of those aged 25–39 years and 23.5% of those aged 40–50 years had not undergone mammography screening for breast cancer, as recommended by current guidelines for survivors of childhood cancer.
doi:10.1001/jama.2008.1039
PMCID: PMC2676434  PMID: 19176442
24.  Activating mutations in ALK provide a therapeutic target in neuroblastoma 
Nature  2008;455(7215):975-978.
Neuroblastoma, an embryonal tumor of the peripheral sympathetic nervous system, accounts for approximately 15% of all deaths due to childhood cancer1. High-risk neuroblastomas, prevalent in the majority of patients, are rapidly progressive; even with intensive myeloablative chemotherapy, relapse is common and almost uniformly fatal2,3. Here we report the detection of previously unknown mutations in the ALK gene, which encodes a receptor tyrosine kinase, in 8% of primary neuroblastomas. Five non-synonymous sequence variations were identified in the kinase domain of ALK, of which three were somatic and two were germline. The most frequent mutation, F1174L, was also identified in three different neuroblastoma cell lines. ALK cDNAs encoding the F1174L and R1275Q variants, but not the wild-type ALK cDNA, transformed IL-3-dependent murine hematopoietic Ba/F3 cells to cytokine-independent growth. Ba/F3 cells expressing these mutations were sensitive to a small-molecule inhibitor of ALK, TAE6844. Furthermore, two human neuroblastoma cell lines harboring the F1174L mutation were sensitive to the inhibitor. Cytotoxicity was associated with increased levels of apoptosis as measured by TUNEL-labeling. shRNA-mediated knockdown of ALK expression in neuroblastoma cell lines with the F1174L mutation also resulted in apoptosis and impaired cell proliferation. Thus, activating alleles of the ALK receptor tyrosine kinase are present in primary neuroblastoma tumors and in established neuroblastoma cell lines, and confer sensitivity to ALK inhibition with small molecules, providing a molecular rationale for targeted therapy of this disease.
doi:10.1038/nature07397
PMCID: PMC2587486  PMID: 18923525
25.  Genome-Wide Analysis of Neuroblastomas using High-Density Single Nucleotide Polymorphism Arrays 
PLoS ONE  2007;2(2):e255.
Background
Neuroblastomas are characterized by chromosomal alterations with biological and clinical significance. We analyzed paired blood and primary tumor samples from 22 children with high-risk neuroblastoma for loss of heterozygosity (LOH) and DNA copy number change using the Affymetrix 10K single nucleotide polymorphism (SNP) array.
Findings
Multiple areas of LOH and copy number gain were seen. The most commonly observed area of LOH was on chromosome arm 11q (15/22 samples; 68%). Chromosome 11q LOH was highly associated with occurrence of chromosome 3p LOH: 9 of the 15 samples with 11q LOH had concomitant 3p LOH (P = 0.016). Chromosome 1p LOH was seen in one-third of cases. LOH events on chromosomes 11q and 1p were generally accompanied by copy number loss, indicating hemizygous deletion within these regions. The one exception was on chromosome 11p, where LOH in all four cases was accompanied by normal copy number or diploidy, implying uniparental disomy. Gain of copy number was most frequently observed on chromosome arm 17q (21/22 samples; 95%) and was associated with allelic imbalance in six samples. Amplification of MYCN was also noted, and also amplification of a second gene, ALK, in a single case.
Conclusions
This analysis demonstrates the power of SNP arrays for high-resolution determination of LOH and DNA copy number change in neuroblastoma, a tumor in which specific allelic changes drive clinical outcome and selection of therapy.
doi:10.1371/journal.pone.0000255
PMCID: PMC1797488  PMID: 17327916

Results 1-25 (25)