[show abstract][hide abstract] ABSTRACT: As advancements in cancer therapies have led to dramatic improvements in long term survival, there has been increasing interest in methods to expand fertility preservation options for cancer patients.
An experimental protocol for ovarian tissue cryopreservation was developed at the University of Pennsylvania for patients requiring gonadotoxic therapies. The protocol for adults was implemented at the Hospital of the University of Pennsylvania and for children at the Children's Hospital of Philadelphia in collaboration with the Oncofertility Consortium and the National Physicians Cooperative (NPC).
A total of twenty-one patients (age range: 8-36 years) have cryopreserved ovarian tissue as part of this study. While patients had a variety of diagnoses and treatment exposures, 10/21 (48 %) patients suffered from hematologic disorders and 43 % were anticipating stem cell transplantation. No patients have requested that the tissue be used for clinical purposes.
Ovarian tissue cryopreservation protocols can be implemented at pediatric and adult institutions through multi-disciplinary collaboration. While more research is needed to determine the safety and efficacy of ovarian tissue cryopreservation, this procedure provides hope for preserving the ability to have biological offspring to patients facing gonadotoxic therapies for a variety of medical conditions.
Journal of Assisted Reproduction and Genetics 04/2012; 29(6):495-502. · 1.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared with healthy controls of similar age and late reproductive age.
Cross-sectional analysis of data from a prospective cohort study.
University medical center.
Seventy-one cancer survivors aged 15-39 years; 67 healthy, similarly aged unexposed subjects; and 69 regularly menstruating women of late reproductive age (40-52 years).
Early follicular-phase hormones (FSH, E(2), inhibin B, antimüllerian hormone [AMH]) and ovarian ultrasound measurements (ovarian volume and antral follicle counts [AFC]) were compared using multivariable linear regression.
In adjusted models, FSH, AMH, and AFC differed between exposed vs. unexposed subjects (FSH 11.12 mIU/mL vs. 7.25 mIU/mL; AMH 0.81 ng/mL vs. 2.85 ng/mL; AFC 14.55 vs. 27.20). In participants with an FSH <10 mIU/mL, survivors had lower levels of AMH and AFC compared with controls. Alkylating agent dose score was associated with increased levels of FSH and decreased levels of AMH. Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC, and ovarian volume. Antimüllerian hormone was similar in women previously exposed to high-dose cancer therapy and 40-42-year-old controls.
Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared with unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to those in late-reproductive-age women. The predictive value of measures for pregnancy and menopause must be studied. CLINICALTRIALS.GOV IDENTIFIER: NCT01143844.
Fertility and sterility 12/2011; 97(1):134-40.e1. · 3.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: In the last decade, 13-cis-retinoic acid (13-cis-RA) has been added to the treatment of patients with high-risk neuroblastoma. In survivors of neuroblastoma, short stature is consistently observed. Causes include growth hormone deficiency and poor growth of irradiated long bones. Within the survivorship program at CHOP, we have observed that a number of these patients also have advanced bone ages. Children treated with 13-cis-RA are at risk for advanced bone age that may dramatically impact their linear growth. Ongoing evaluation is necessary to examine the effect of 13-cis-RA on final adult height and to inform clinical practice in this cohort.
Pediatric Blood & Cancer 11/2010; 56(3):474-6. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adolescent and young adult survivors of childhood cancer are a vulnerable population. Health beliefs may be related to necessary follow-up care.
This study seeks to develop a measure of health beliefs for adolescents and young adults with and without a history of cancer.
Inductive and deductive methods and focus groups were used to develop the Health Competence Beliefs Inventory. Cancer survivors (n = 138) and comparison participants (n = 130) completed the Health Competence Beliefs Inventory and other measures. Healthcare providers reported current medical problems.
A series of iterative exploratory factor analyses generated a 21-item four-factor solution: (1) Health Perceptions; (2) Satisfaction with Healthcare; (3) Cognitive Competence; and (4) Autonomy. Survivors reported significantly different Health Competence Beliefs Inventory scale scores than comparisons (p < .05). The Health Competence Beliefs Inventory was associated with beliefs, affect, quality of life, posttraumatic stress symptoms, and medical problems.
The Health Competence Beliefs Inventory is a promising measure of adolescent and young adult perceptions of health and well-being.
Annals of Behavioral Medicine 10/2010; 41(1):48-58. · 4.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE The purpose of this study was to compare adolescent and young adult (AYA) pediatric cancer survivors and peers without a history of serious illness on psychological distress, health-related quality of life (HRQOL), health beliefs; examine age at diagnosis and cancer treatment intensity on these outcomes; and examine relationships between number of health problems and the outcomes. PATIENTS AND METHODS AYA cancer survivors (n = 167) and controls (n = 170), recruited during visits to a cancer survivorship clinic and primary care, completed self-report questionnaires of distress, health problems, and health beliefs. For survivors, providers rated treatment intensity and health problems. Results There were no statistically significant differences between survivors and controls in psychological distress or HRQOL. Cancer survivors had less positive health beliefs. Survivors diagnosed as adolescents had significantly greater psychological distress and fewer positive health beliefs than those diagnosed earlier. Survivors with the highest level of treatment intensity had greater anxiety and fewer positive health beliefs than those with less intense treatments. Provider report of current health problems related to survivors' beliefs and mental HRQOL only, whereas patient report of health problems correlated significantly with most psychosocial outcomes and beliefs. CONCLUSION AYA cancer survivors did not differ from peers in psychological adjustment but did endorse less adaptive health beliefs. Survivors diagnosed during adolescence and who had more intensive cancer treatments evidenced poorer psychosocial outcomes. Beliefs about health may be identified and targeted for intervention to improve quality of life, particularly when patient perceptions of current health problems are considered.
Journal of Clinical Oncology 03/2010; 28(12):2002-7. · 18.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Increasing numbers of childhood cancer survivors are being seen in primary care settings as young adults. It is unknown how their self-reported health problems differ from those of healthy young adults. Self-reported health problems of cancer survivors and healthy controls are compared in this study.
156 cancer survivors visiting a cancer survivorship program and 138 controls in primary care centers (mean age, 20 years) completed the Health Knowledge Inventory, a checklist of 35 health problems.
Cancer survivors reported significantly more health problems than healthy controls (5.6 vs 2.6 problems; P < .001). For cancer survivors, more intense treatment and older age related to Organic/Major problems and Constitutional/Other problems. Female sex related to report of Organic/Major problems and Constitutional/Other problems for the controls. Although at least 20% of both healthy controls and survivors endorsed dermatologic, headache, gastrointestinal, and weight problems, survivors endorsed growth, thyroid, kidney, immunologic, heart, and fertility problems 4-fold over controls.
Cancer survivors endorse significantly more health problems than do healthy controls. However, some problems are reported with equal frequency among the groups. Understanding these similarities and differences between survivors and healthy controls will facilitate patient-centered comprehensive care for young-adult cancer survivors.
The Journal of the American Board of Family Medicine 01/2010; 23(3):306-14. · 1.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: In the human testis, beginning at approximately 2 months of age, gonocytes are replaced by adult dark (Ad) and pale (Ap) spermatogonia that make up the spermatogonial stem cell (SSC) pool. In mice, the SSC pool arises from gonocytes approximately 6 days after birth. During puberty in both species, complete spermatogenesis is established by cells that differentiate from SSCs. Essentially pure populations of prepubertal human spermatogonia and mouse gonocytes were selected from testis biopsies and validated by confirming the presence of specific marker proteins in cells. Stem cell potential of germ cells was demonstrated by transplantation to mouse testes, following which the cells migrated to the basement membrane of the seminiferous tubule and were maintained similar to SSCs. Differential gene expression profiles generated between germ cells and testis somatic cells demonstrated that expression of genes previously identified as SSC and spermatogonial-specific markers (e.g., zinc-finger and BTB-domain containing 16, ZBTB16) was greatly elevated in both human spermatogonia and mouse gonocytes compared to somatic cells. Several genes were expressed at significantly higher levels in germ cells of both species. Most importantly, genes known to be essential for mouse SSC self-renewal (e.g., Ret proto-oncogene, Ret; GDNF-family receptor alpha1, Gfr alpha1; and B-cell CLL/lymphoma 6, member B, Bcl6b) were more highly expressed in both prepubertal human spermatogonia and mouse gonocytes than in somatic cells. The results indicate remarkable conservation of gene expression, notably for self-renewal genes, in these prepubertal germline cells between two species that diverged phylogenetically approximately 75 million years ago.
Proceedings of the National Academy of Sciences 12/2009; 106(51):21672-7. · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gonadal damage is a consequence of therapy for pediatric malignancies. Prepubertal males have no semen or mature spermatozoa, posing a challenge for fertility preservation. Testicular tissue cryopreservation is a potential option but is still experimental. We report on a pilot protocol that offered testicular biopsy cryopreservation to families of prepubertal boys with newly diagnosed malignancy. The aims were to determine the acceptability and safety of this procedure.
Parents of prepubertal boys with diagnoses at highest risk for treatment-related gonadal damage were offered the option of testicular cryopreservation. Half of the biopsy was frozen for the subject's potential future use and the remainder used for research. Data on negative intraoperative and/or 7 day post-operative sequelae of testicular biopsies were assessed. Two to four weeks later, parents were asked to complete a questionnaire on factors influencing their decision to have the biopsy or not.
Since January 2008, 24 boys have met the eligibility criteria but three required immediate treatment and were excluded. Sixteen of 21 families (76%) consented to testicular biopsy, indicating the prospective acceptability of this option to parents of boys aged 3 months to 14 years; 14 underwent the procedure without any negative intra- or post-operative sequelae. Although the time at diagnosis is stressful, families can give thoughtful consideration to this option. Factors such as religion, finance, ethics and the experimental nature of cryopreservation did not play a major role in decision-making.
Parents of prepubertal boys with cancer are willing to pursue testicular tissue cryopreservation at diagnosis, and testicular biopsy caused no acute adverse effects.
Human Reproduction 10/2009; 25(1):37-41. · 4.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Increasing numbers of children with advanced neuroblastoma are achieving cure. We describe the clinical late effects specific to survivors of stage IV neuroblastoma all similarly treated using tandem autologous peripheral blood stem cell rescue with TBI.
The medical records of 35 neuroblastoma patients treated at CHOP between 1997 and 2001 were examined. Eighteen of the 35 patients died of progressive disease, and 4 were lost to follow-up. Thirteen patients continue to follow-up in our Multidisciplinary Cancer Survivorship Clinic where they are evaluated and monitored by a consistent group of subspecialists that evaluate long-term sequelae. Data on treatment exposures including TBI and treatment related sequelae identified by clinician assessment and/or diagnostic testing were collected.
Results indicate late effects were present in all 13 subjects, 12 of whom suffered from multiple negative sequelae, including issues with growth hormone deficiency, dental problems, osteochondromas and hearing deficiencies, among others, most at higher rates than reported previously.
The findings in this small cohort indicate the need for future prospective studies of this intensive pediatric cancer treatment, and underscore the importance of medical intervention and long-term monitoring of these at-risk subjects to increase overall quality-of-life.
Pediatric Blood & Cancer 08/2008; 51(5):679-83. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Infertility is often a complication for adolescent and young adult males who receive cancer therapy, a problem that might be averted through using cryopreserved sperm. We aim to evaluate feasibility of offering newly diagnosed patients the opportunity to bank sperm and, to determine the beliefs and decision-making processes of patients and their parents who considered sperm banking.
Eligible patients and parents were approached and offered sperm cryopreservation. Semen samples from patients who sequentially attempted sperm banking were analyzed. Questionnaires were then administered to patients and parents who had been approached about sperm banking.
Semen samples from 68 patients were analyzed. Nine patients were azoospermic; all had been pre-treated with chemotherapy. Fifty patients completed the questionnaire. Parent and patient made the decision together to bank 80% of the time. All sons who attempted to bank and their parents felt they had made the right decision, including those who attempted but failed.
Viable sperm can be collected successfully from adolescent and young adults who are newly diagnosed with cancer. Semen quality was dramatically reduced by one course of gonadotoxic therapy. Parents and patients want information regarding sperm cryopreservation early. Parents appear to play an important role in the decision to sperm bank. We recommend sperm banking be offered to all eligible patients.
Pediatric Blood & Cancer 04/2008; 50(3):594-8. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Long-term survival for children with cancer is often achieved at a considerable cost in terms of medical and psychological sequelae. Although many survivors are well and require only routine follow-up and surveillance, a cohort of survivors require comprehensive management of complex, chronic medical issues by multiple subspecialists. For these survivors, care delivered within the context of an annual visit to a traditional hospital-based late effects clinic or by a primary care physician in the community is often not adequate. A specialized clinic was implemented at The Children's Hospital of Philadelphia that crosses disciplines and provides same-day, same-clinic access to oncology/survivorship, endocrinology, pulmonology, cardiology, nutrition, and psychology. This multidisciplinary approach supports clinical efficiency and fosters seamless patient-centered care both for patients with identified late effects and for those with the highest risk for problems because of intense treatment exposures. The model is described with a focus on clinic structure/process, clinical outcomes, and benefits to survivor, health care provider, and institution. The diverse roles for nursing within this model are highlighted.
[show abstract][hide abstract] ABSTRACT: Comparison of functional mobility and quality of life is performed in patients with lower-extremity bone sarcoma following either amputation, limb-sparing surgery, or rotationplasty with four different types of outcome measures: (1) an objective functional mobility measure that requires patients to physically perform specific tasks, functional mobility assessment (FMA); (2) a clinician administered tool, Musculoskeletal Tumor Society Scale (MSTS); (3) a patient questionnaire, Toronto Extremity Salvage Scale (TESS); and (4) a health-related quality of life (HRQL) measure, Short Form-36 version 2 (SF-36v.2).
This is a prospective multi-site study including 91 patients with lower-extremity bone sarcoma following amputation, limb-sparing surgery, or rotationplasty. One of three physical therapists administered the quality of life measure (SF-36v.2) as well as a battery of functional measures (FMA, MSTS, and TESS).
Differences between patients who had amputation, limb-sparing surgery, or rotationplasty were consistently demonstrated by the FMA. Patients with limb sparing femur surgery performed better than those patients with an above the knee amputation but similarly to a small number of rotationplasty patients. Several of the more conventional self-report measures were shown to not have the discriminative capabilities of the FMA in these cohorts.
In adolescents with lower-extremity bone sarcoma, it may be advantageous to consider the use of a combination of outcome measures, including the FMA, for objective functional mobility assessment along with the TESS for a subjective measure of disability and the SF-36v.2 for a quality-of-life measure.
Pediatric Blood & Cancer 01/2008; 49(7):964-9. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent advances in diagnostic and therapeutic methods in pediatric oncology have led to greater survival rates in children with malignancies. However, major long-term complications can occur that limit the quality of survival, infertility being one of them. Chemotherapy, radiation treatment, surgery, and combinations of these treatments have been implicated in causing infertility, with males being especially sensitive to therapy. Cryopreservation of semen, or sperm banking, is an easy, widely available means to preserve fertility for adolescent and young adult males with cancer. In this article, the pertinent literature is reviewed, and a sperm-banking program is described. Recommendations are offered for institutions attempting to develop a successful program, and the nurse's role in education and facilitation is discussed.
[show abstract][hide abstract] ABSTRACT: Reliability and validity of a new tool, Functional Mobility Assessment (FMA), were examined in patients with lower-extremity sarcoma. FMA requires the patients to physically perform the functional mobility measures, unlike patient self-report or clinician administered measures.
A sample of 114 subjects participated, 20 healthy volunteers and 94 patients with lower-extremity sarcoma after amputation, limb-sparing, or rotationplasty surgery. Reliability of the FMA was examined by three raters testing 20 healthy volunteers and 23 subjects with lower-extremity sarcoma. Concurrent validity was examined using data from 94 subjects with lower-extremity sarcoma who completed the FMA, Musculoskeletal Tumor Society (MSTS), Short-Form 36 (SF-36v2), and Toronto Extremity Salvage Scale (TESS) scores. Construct validity was measured by the ability of the FMA to discriminate between subjects with and without functional mobility deficits.
FMA demonstrated excellent reliability (ICC [2,1] >or=0.97). Moderate correlations were found between FMA and SF-36v2 (r = 0.60, P < 0.01), FMA and MSTS (r = 0.68, P < 0.01), and FMA and TESS (r = 0.62, P < 0.01). The patients with lower-extremity sarcoma scored lower on the FMA as compared to healthy controls (P < 0.01).
The FMA is a reliable and valid functional outcome measure for patients with lower-extremity sarcoma. This study supports the ability of the FMA to discriminate between patients with varying functional abilities and supports the need to include measures of objective functional mobility in examination of patients with lower-extremity sarcoma.
Pediatric Blood & Cancer 08/2007; 49(2):183-9. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: We sought to determine the prevalence of abnormal pulmonary function tests (PFTs) in a cohort of children who had received whole lung irradiation (WLI) for treatment of metastatic disease.
This was a retrospective (1988-2003) chart review that included all children treated at our institution with WLI who had undergone PFT. Data abstracted included oncologic diagnosis, radiation dose and fractionation, spirometry (FVC, FEV1, FEV1/FVC, FEF25%-75%), plethysmography (TLC, FRC, RV, RV/TLC), diffusing capacity (DLCO), and respiratory muscle strength (MIP, MEP). PFTs were normalized according to standard deviation (Z) scores.
Thirty patients were identified who had one or more PFT. The incidence of mild, moderate, or severe reductions in FEV1 was 30%, 10%, and 10%, respectively, with 50% having normal FEV1. Seventeen percent of patients had mild reduction in total lung capacity (TLC), while 13% and 30% had moderate or severe reductions. Thirty-eight percent had mild reductions in diffusing capacity, while 29% and 14% had moderate or severe reductions.
Pulmonary function abnormalities were common in this cohort of children treated with WLI, and may be progressive in nature. Further studies are warranted to identify patients at highest risk.
Pediatric Blood & Cancer 03/2006; 46(2):222-7. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: One of the major challenges faced by young adult survivors of childhood cancer is the transition from a specialized pediatric care facility to adult-based health care that provides appropriate follow-up. This review summarizes the issues regarding the necessity of this transition, including a brief history of follow-up care of childhood cancer survivors. The general principles of transition care, as well as the barriers and obstacles specific to this population are outlined with the advantages and limitations of several models of transition care that could be considered.
Pediatric Blood & Cancer 03/2006; 46(2):169-73. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: The study was designed to examine relationships between range of motion (ROM), functional mobility, and quality of life (QL) in patients with lower-extremity sarcoma (LES) after limb-sparing surgery
Sixty-eight patients with LES (age, 10-26 years) participated. The patients performed hip flexion, hip extension, knee flexion, and knee extension, Timed Up and Down Stairs (TUDS), Timed Up and Go (TUG), nine-minute run-walk (9-min), and completed the QL measure, Short-Form-36 version two (SF-36v2).
Significant correlations (p < 0.01) were found between hip extension and SF-36v2 physical component scale (PCS; r = 0.33), TUDS (r = -0.32), TUG (r = -0.33); hip flexion and TUDS (r = -0.31), TUG (r = -0.39), 9-min (r = 0.44); knee flexion and TUDS (r = -0.52), TUG (r = -0.40), 9-min (r = 0.37); SF-36v2 PCS and TUDS (r = -0.56), TUG (r = -0.51), 9-min (r = 0.60).
ROM correlates with functional mobility and QL in patients with LES after limb-sparing surgery. ROM exercises are important component of a physical therapy program for children and adolescents with LES.
[show abstract][hide abstract] ABSTRACT: More than 80% of those diagnosed with Hodgkins disease (HD) will survive long-term. For the past decade, a modified hybrid consisting of cyclophosphamide (2.4-3.6g/m(2)), vincristine, procarbazine, and prednisone (COPP) together with adriamycin, bleomycin, and vinblastine (ABV) has been used to treat patients with HD. Little data exists on how this modified hybrid impacts male fertility. Eleven male patients treated with COPP-ABV hybrid were studied. Nine out of 11 subjects were categorized as infertile by semen analysis; 7 of 9 were azoospermic. There was no association between fertility status and prepubertal status at diagnosis or gonadotropin status. Despite lower doses of cyclophosphamide, treatment with the current COPP/ABV hybrid leads to infertility in the majority of young men. It is likely that procarbazine, an effective yet potent gonadotoxic agent, is responsible for this outcome.
Pediatric Blood & Cancer 03/2005; 44(2):193-6. · 2.35 Impact Factor