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1.  Early aging in adult survivors of childhood medulloblastoma: long-term neurocognitive, functional, and physical outcomes 
Neuro-Oncology  2011;13(5):536-545.
Treatment for medulloblastoma during childhood impairs neurocognitive function in survivors. While those diagnosed at younger ages are most vulnerable, little is known about the long-term neurocognitive, functional, and physical outcomes in survivors as they approach middle age. In this retrospective cohort study, we assessed 20 adults who were treated with surgery and radiotherapy for medulloblastoma during childhood (median age at assessment, 21.9 years [range, 18–47 years]; median time since diagnosis, 15.5 years [range, 6.5–42.2 years]). Nine patients also underwent chemotherapy. Cross-sectional analyses of current neurocognitive, functional, and physical status were conducted. Data from prior neuropsychological assessments were available for 18 subjects; longitudinal analyses were used to model individual change over time for those subjects. The group was well below average across multiple neurocognitive domains, and 90% had required accommodations at school for learning disorders. Longer time since diagnosis, but not age at diagnosis, was associated with continued decline in working memory, a common sign of aging. Younger age at diagnosis was associated with lower intelligence quotient and academic achievement scores, even many years after treatment had been completed. The most common health complications in survivors were hearing impairment, second cancers, diabetes, hypertension, and endocrine deficiencies. Adult survivors of childhood medulloblastoma exhibit signs of early aging regardless of how young they were at diagnosis. As survival rates for brain tumors continue to improve, these neurocognitive and physical sequelae may become evident in survivors diagnosed at different ages across the lifespan. It will become increasingly important to identify factors that contribute to risk and resilience in this growing population.
PMCID: PMC3093335  PMID: 21367970
brain tumor; late effects; neuropsychology; pediatric cancer; radiation
2.  Impact of Low-Dose Involved-Field Radiation Therapy on Pediatric Patients with Lymphocyte-Predominant Hodgkin Lymphoma Treated with Chemotherapy: A Report from the Children’s Oncology Group 
Pediatric blood & cancer  2012;59(7):1284-1289.
Treatment of pediatric lymphocyte-predominant Hodgkin lymphoma (LPHL) is controversial but has typically consisted of both chemotherapy and radiation. Radiation therapy is associated with potential late effects in children and adolescents. We examined the impact of radiation therapy on long-term outcome of patients with LPHL treated on CCG-5942, a large pediatric cooperative group study of Hodgkin lymphoma.
Eighty-two patients with LPHL were registered on CCG-5942. Fifty-two patients (63%) received chemotherapy alone; 29 patients (35%) received chemotherapy followed by involved-field radiation therapy (IFRT).
The median follow-up of the LPHL patients is 7.7 years; 63 patients (77%) have > 5 years of follow-up. The 5-year event-free survival (EFS) and overall survival (OS) were 97% and 100%. Two relapses occurred, both in patients who did not receive IFRT. There were no significant differences in EFS or OS between patients who received or did not receive IFRT.
This subset analysis demonstrates the chemosensitivity of pediatric LPHL. Patients who had a complete response to chemotherapy had an excellent EFS and OS without the addition of radiotherapy.
PMCID: PMC3468707  PMID: 22847767
Lymphocyte-Predominant Hodgkin Lymphoma
3.  Navigator channel adaptation to reconstruct three dimensional heart volumes from two dimensional radiotherapy planning data 
BMC Medical Physics  2012;12:1.
Biologically-based models that utilize 3D radiation dosimetry data to estimate the risk of late cardiac effects could have significant utility for planning radiotherapy in young patients. A major challenge arises from having only 2D treatment planning data for patients with long-term follow-up. In this study, we evaluate the accuracy of an advanced deformable image registration (DIR) and navigator channels (NC) adaptation technique to reconstruct 3D heart volumes from 2D radiotherapy planning images for Hodgkin's Lymphoma (HL) patients.
Planning CT images were obtained for 50 HL patients who underwent mediastinal radiotherapy. Twelve image sets (6 male, 6 female) were used to construct a male and a female population heart model, which was registered to 23 HL "Reference" patients' CT images using a DIR algorithm, MORFEUS. This generated a series of population-to-Reference patient specific 3D deformation maps. The technique was independently tested on 15 additional "Test" patients by reconstructing their 3D heart volumes using 2D digitally reconstructed radiographs (DRR). The technique involved: 1) identifying a matching Reference patient for each Test patient using thorax measurements, 2) placement of six NCs on matching Reference and Test patients' DRRs to capture differences in significant heart curvatures, 3) adapting the population-to-Reference patient-specific deformation maps to generate population-to-Test patient-specific deformation maps using linear and bilinear interpolation methods, 4) applying population-to-Test patient specific deformation to the population model to reconstruct Test-patient specific 3D heart models. The percentage volume overlap between the NC-adapted reconstruction and actual Test patient's true heart volume was calculated using the Dice coefficient.
The average Dice coefficient expressed as a percentage between the NC-adapted and actual Test model was 89.4 ± 2.8%. The modified NC adaptation technique made significant improvements to the population deformation heart models (p = 0.01). As standard evaluation, the residual Dice error after adaptation was comparable to the volumetric differences observed in free-breathing heart volumes (p = 0.62).
The reconstruction technique described generates accurate 3D heart models from limited 2D planning data. This development could potentially be used to retrospectively calculate delivered dose to the heart for historically treated patients and thereby provide a better understanding of late radiation-related cardiac effects.
PMCID: PMC3398341  PMID: 22257738
4.  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.
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.
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.
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.
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.
PMCID: PMC3114793  PMID: 21569345
5.  Population-Based Longitudinal Study of Follow-Up Care for Breast Cancer Survivors 
Journal of Oncology Practice  2010;6(4):174-181.
This study shows substantial variation in adherence to guideline recommendations, with both overuse and underuse of surveillance visits and tests.
To describe the patterns of follow-up care provided to a population-based cohort of breast cancer survivors, and to assess factors associated with adherence to guidelines on follow-up care.
Patients and Methods:
We conducted a retrospective longitudinal study of all women with surgically treated breast cancer who were without evidence of recurrence, advanced breast cancer, or new primary cancer and were diagnosed in Ontario, Canada, within a 2-year period (n = 11,219). They were followed for 5 years. The cohort was identified through the Ontario Cancer Registry, and individuals were linked across population-based administrative health databases. Frequency of and adherence to guideline recommendations for oncologist and primary care physician (PCP) visits; surveillance imaging for metastatic disease; and surveillance mammograms by year from diagnosis, age group, and income quintile were analyzed. Factors associated with adherence to guideline recommendations were analyzed.
Most women saw both oncologists and PCPs in each follow-up year. Approximately two thirds had surveillance mammograms in each follow-up year. Overall, two thirds had either fewer or greater than recommended oncology visits, one quarter had fewer than recommended surveillance mammograms, and half had greater than recommended surveillance imaging for metastatic disease.
This population-based study shows substantial variation in adherence to guideline recommendations, with both overuse and underuse of surveillance visits and tests. Most importantly, a substantial proportion are receiving more than recommended imaging for metastatic disease but fewer than recommended mammograms for detection of local recurrence or new primary cancer, for which effective intervention is possible.
PMCID: PMC2900866  PMID: 21037867
6.  Cancer screening practices of cancer survivors 
Canadian Family Physician  2012;58(9):980-986.
To describe cancer screening rates for cancer survivors and compare them with those for matched controls.
Population-based, retrospective study with individuals linked across administrative databases.
Survivors of breast (n = 11 219), colorectal (n = 4348), or endometrial (n = 3473) cancer, or Hodgkin lymphoma (HL) (n = 2071) matched to general population controls. Survivors were those who had completed primary treatment and were on “well” follow-up. The study period was 4 years (1 to 5 years from the date of cancer diagnosis).
Main outcome measures
Never versus ever screened (in the 4-year study period) for breast cancer, colorectal cancer (CRC), and cervical cancer and never versus ever received (during the study period) a periodic health examination; rates were compared between cancer survivors and controls. Random effects models were used to estimate odds ratios and 95% CIs.
Sixty-five percent of breast cancer survivors were never screened for CRC and 40% were never screened for cervical cancer. Approximately 50% of CRC survivors were never screened for breast or cervical cancer. Thirty-two percent of endometrial cancer survivors were never screened for breast cancer and 66% were never screened for CRC. Forty-four percent of HL survivors were never screened for breast cancer, 77% were never screened for CRC, and 32% were never screened for cervical cancer. Comparison with matched controls showed a mixed picture, with breast and endometrial cancer survivors more likely, and CRC and HL survivors less likely, than controls to be screened.
There is concern about the preventive care of cancer survivors despite frequent visits to both oncology specialists and family physicians during the “well” follow-up period.
PMCID: PMC3440276  PMID: 22972732
7.  A national survey of the availability of intensity-modulated radiation therapy and stereotactic radiosurgery in Canada 
The timely and appropriate adoption of new radiation therapy (RT) technologies is a challenge both in terms of providing of optimal patient care and managing health care resources. Relatively little is known regarding the rate at which new RT technologies are adopted in different jurisdictions, and the barriers to implementation of these technologies.
Surveys were sent to all radiation oncology department heads in Canada regarding the availability of RT equipment from 2006 to 2010. Data were collected concerning the availability and use of Intensity Modulated Radiation Therapy (IMRT) and stereotactic radiosurgery (SRS), and the obstacles to implementation of these technologies.
IMRT was available in 37% of responding centers in 2006, increasing to 87% in 2010. In 2010, 72% of centers reported that IMRT was available for all patients who might benefit, and 37% indicated that they used IMRT for "virtually all" head and neck patients. SRS availability increased from 26% in 2006 to 42.5% in 2010. Eighty-two percent of centers reported that patients had access to SRS either directly or by referral. The main barriers for IMRT implementation included the need to train or hire treatment planning staff, whereas barriers to SRS implementation mostly included the need to purchase and/or upgrade existing planning software and equipment.
The survey showed a growing adoption of IMRT and SRS in Canada, although the latter was available in less than half of responding centers. Barriers to implementation differed for IMRT compared to SRS. Enhancing human resources is an important consideration in the implementation of new RT technologies, due to the multidisciplinary nature of the planning and treatment process.
PMCID: PMC3339388  PMID: 22309806
intensity-modulated radiation therapy; stereotactic radiosurgery; survey
8.  A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk 
Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk.
Organ-specific dose-volume histograms (DVH) were generated for 41 patients receiving 35 Gy mantle RT, 35 Gy IFRT, or 20 Gy IFRT, and integrated organ mean doses were compared for the three protocols. Organ-specific SC risk estimates were estimated using a dosimetric risk-modeling approach, analyzing DVH data with quantitative, mechanistic models of radiation-induced cancer.
Dose reductions resulted in corresponding reductions in predicted excess relative risks (ERR) for SC induction. Moving from 35 Gy mantle RT to 35 Gy IFRT reduces predicted ERR for female breast and lung cancer by approximately 65%, and for male lung cancer by approximately 35%; moving from 35 Gy IFRT to 20 Gy IFRT reduces predicted ERRs approximately 40% more. The median reduction in integral dose to the whole heart with the transition to 35 Gy IFRT was 35%, with a smaller (2%) reduction in dose to proximal coronary arteries. There was no significant reduction in thyroid dose.
The significant decreases estimated for radiation-induced SC risks associated with modern IFRT provide strong support for the use of IFRT to reduce the late effects of treatment. The approach employed here can provide new insight into the risks associated with contemporary IFRT for HL, and may facilitate the counseling of patients regarding the risks associated with this treatment.
PMCID: PMC1847517  PMID: 17362522

Results 1-8 (8)