Late effects in survivors of high-risk neuroblastoma following stem cell transplant with and without total body irradiation.

2021

e29537

2021 Dec 31

1545-5017

<p><strong>BACKGROUND: </strong>Neuroblastoma is the most common extracranial solid tumor in children. Those with high-risk disease are treated with multimodal therapy, including high-dose chemotherapy, stem cell transplant, radiation, and immunotherapy that have led to multiple long-term complications in survivors. In the late 1990s, consolidation therapy involved myeloablative conditioning including total body irradiation (TBI) with autologous stem cell rescue. Recognizing the significant long-term toxicities of exposure to TBI, more contemporary treatment protocols have removed this from conditioning regimens. This study examines an expanded cohort of 48 high-risk neuroblastoma patients to identify differences in the late effect profiles for those treated with TBI and those treated without TBI.</p>

<p><strong>PROCEDURE: </strong>Data on the study cohort were collected from clinic charts, provider documentation in the electronic medical record of visits to survivorship clinic, including all subspecialists, and ancillary reports of laboratory and diagnostic tests done as part of risk-based screening at each visit.</p>

<p><strong>RESULTS: </strong>All 48 survivors of BMT for high-risk neuroblastoma had numerous late effects of therapy, with 73% having between five and 10 late effects. TBI impacted some late effects significantly, including growth hormone deficiency (GHD), bone outcomes, and cataracts.</p>

<p><strong>CONCLUSION: </strong>Although high-risk neuroblastoma survivors treated with TBI have significant late effects, those treated without TBI also continue to have significant morbidity related to high-dose chemotherapy and local radiation. A multidisciplinary care team assists in providing comprehensive care to those survivors who are at highest risk for significant late effects.</p>

10.1002/pbc.29537

Pediatr Blood Cancer

34971017

Kidney Outcomes and Hypertension in Survivors of Wilms Tumor: A Prospective Cohort Study.

2020

2020 Dec 05

1097-6833

<p>Supported by a Pilot Grant from the Children's Hospital of Philadelphia Center for Pediatric Clinical Effectiveness (to D.C.). D.C. is also supported by the NIH/NIDDK (K23 DK125670). G.T. was supported by the NIH/NIDDK (K23 DK106428). Ja.G. was supported by NIH/NIDDK (K08 DK110536). M.D. was supported by the NIH/NIDDK (K23 DK093556). The NIH and NIDDK had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the official view of the NIDDK nor NIH. G.T. serves on the scientific advisory boards for Allena Pharmaceuticals, Novome Biotechnology, and Dicerna Pharmaceuticals and serves as a consultant for Alnylam Pharmaceuticals, all of which are unrelated to this work. M.D. receives research funding from Mallinckrodt unrelated to this work. The other authors declare no conflicts of interest. Portions of this study were presented at the Pediatric Academic Society annual meeting, May 5-8, 2020, Toronto, Canada.</p>

<p><strong>OBJECTIVE: </strong>To assess the prevalence of therapy-related kidney outcomes in survivors of Wilms tumor (WT).</p>

<p><strong>STUDY DESIGN: </strong>This prospective cohort study included survivors of WT who were ≥5 years old and ≥1 year from completing therapy, excluding those with pre-existing hypertension, prior dialysis or kidney transplant. Participants completed 24-hour ambulatory blood pressure monitoring (ABPM). Abnormal blood pressure (BP) was defined as ≥90 percentile. Masked hypertension was defined as having normal office BP and abnormal ABPM findings. Urine was analyzed for KIM-1, IL-18, EGF, albumin, and creatinine. Estimated glomerular filtration rate (eGFR) was calculated using the bedside CKiD equation. Recent kidney ultrasounds and echocardiograms were reviewed for contralateral kidney size and left ventricular hypertrophy (LVH), respectively. Clinical follow-up data was collected for approximately 2 years following study enrollment.</p>

<p><strong>RESULTS: </strong>Thirty-two participants (median age 13.6 [IQR: 10.5-16.3] years; 75% ≥Stage 3 WT) were evaluated at a median of 8.7 years (IQR: 6.5-10.8) post-therapy; 29 participants underwent unilateral radical nephrectomy, two bilateral partial nephrectomy, and one radical and contralateral partial nephrectomy. 72% received kidney radiotherapy and 75% received doxorubicin. Recent median eGFR was 95.6 ml/min/1.73m (IQR: 84.6-114.0; 11 (34%) had an eGFR &lt;90). Abnormal ABPM results were found in 22/29 participants (76%), masked hypertension in 10/29 (34%), and microalbuminuria in 2/32 (6%). 22/32 (69%) participants had abnormal EGF; few had abnormal KIM-1 or IL-18. Seven participants with previous unilateral nephrectomy lacked compensatory contralateral kidney hypertrophy. None had LVH.</p>

<p><strong>CONCLUSION: </strong>In survivors of WT, adverse kidney outcomes were common and should be closely monitored.</p>

10.1016/j.jpeds.2020.12.005

J Pediatr

33290810

Attitudes Toward Fertility Preservation Among Transgender Youth and Their Parents.

2020

2020 Apr 29

1879-1972

<p><strong>PURPOSE: </strong>While gender-affirming hormones (GAH) may impact the fertility of transgender and gender diverse (TGGD) youth, few pursue fertility preservation (FP). The objective of this study is to understand youth and parent attitudes toward FP decision-making.</p>

<p><strong>METHODS: </strong>This study is a cross-sectional survey of youth and parents in a pediatric, hospital-based gender clinic from April to December 2017. Surveys were administered electronically, containing 34 items for youth and 31 items for parents regarding desire for biological children, willingness to delay GAH for FP, and factors influencing FP decisions.</p>

<p><strong>RESULTS: </strong>The mean age of youth (n&nbsp;= 64) was 16.8&nbsp;years, and 64% assigned female at birth; 46 parents participated. Few youth (20%) and parents (13%) found it important to have biological children or grandchildren, and 3% of youth and 33% of parents would be willing to delay GAH for FP. The most common factor influencing youth FP decision-making was discomfort with a body part they do not identify with (69%), and for the parents, whether it was important to their child (61%). In paired analyses, youth and their parents answered similarly regarding youth desire for biological children and willingness to delay GAH for FP.</p>

<p><strong>CONCLUSIONS: </strong>The majority of TGGD youth and parents did not find having biological offspring important and were not willing to delay GAH for FP. Discomfort with reproductive anatomy was a major influencing factor for youth FP decision-making and their child's wishes was a major factor for parents. Future qualitative research is needed to understand TGGD youth and parent attitudes toward FP and to develop shared decision-making tools.</p>

10.1016/j.jadohealth.2020.02.027

J Adolesc Health

32359942

Development and Content Validation of the Transition Readiness Inventory Item Pool for Adolescent and Young Adult Survivors of Childhood Cancer.

2017

983-994

2017 Oct 01

1465-735X

<p><strong>Objective: </strong>The development of the Transition Readiness Inventory (TRI) item pool for adolescent and young adult childhood cancer survivors is described, aiming to both advance transition research and provide an example of the application of NIH Patient Reported Outcomes Information System methods.</p>

<p><strong>Methods: </strong>Using rigorous measurement development methods including mixed methods, patient and parent versions of the TRI item pool were created based on the Social-ecological Model of Adolescent and young adult Readiness for Transition (SMART).</p>

<p><strong>Results: </strong>Each stage informed development and refinement of the item pool. Content validity ratings and cognitive interviews resulted in 81 content valid items for the patient version and 85 items for the parent version.</p>

<p><strong>Conclusions: </strong>TRI represents the first multi-informant, rigorously developed transition readiness item pool that comprehensively measures the social-ecological components of transition readiness. Discussion includes clinical implications, the application of TRI and the methods to develop the item pool to other populations, and next steps for further validation and refinement.</p>

10.1093/jpepsy/jsx095

J Pediatr Psychol

29046041

Childhood cancer survivors exposed to total body irradiation are at significant risk for slipped capital femoral epiphysis during recombinant growth hormone therapy.

2013

1766-71

2013 Nov

1545-5017

<p><strong>BACKGROUND: </strong>Childhood cancer survivors treated with cranial or total body irradiation (TBI) are at risk for growth hormone deficiency (GHD). Recombinant growth hormone (rhGH) therapy is associated with slipped capital femoral epiphysis (SCFE). We compared the incidence of SCFE after TBI versus cranial irradiation (CI) in childhood cancer survivors treated with rhGH.</p>

<p><strong>PROCEDURE: </strong>Retrospective cohort study (1980-2010) of 119 survivors treated with rhGH for irradiation-induced GHD (56 TBI; 63 CI). SCFE incidence rates were compared in CI and TBI recipients, and compared with national registry SCFE rates in children treated with rhGH for idiopathic GHD.</p>

<p><strong>RESULTS: </strong>Median survivor follow-up since rhGH initiation was 4.8 (range 0.2-18.3) years. SCFE was diagnosed in 10 subjects post-TBI and none after CI (P &lt; 0.001). All 10 subjects had atypical valgus SCFE, and 7 were bilateral at presentation. Within TBI recipients, age at cancer diagnosis, sex, race, underlying malignancy, age at radiation, and age at initiation of rhGH did not differ significantly between those with versus without SCFE. The mean (SD) age at SCFE diagnosis was 12.3 (2.7) years and median duration of rhGH therapy to SCFE was 1.8 years. The SCFE incidence rate after TBI exposure was 35.9 per 1,000 person years, representing a 211-fold greater rate than reported in children treated with rhGH for idiopathic GH deficiency.</p>

<p><strong>CONCLUSIONS: </strong>The markedly greater SCFE incidence rate in childhood cancer survivors with TBI-associated GHD, compared with rates in children with idiopathic GHD, suggests that cancer treatment effects to the proximal femoral physis may contribute to SCFE.</p>

10.1002/pbc.24667

Pediatr Blood Cancer

23818448

Associates of Engagement in Adult-Oriented Follow-Up Care for Childhood Cancer Survivors.

2017

147-153

2017 Feb

1879-1972

<p><strong>PURPOSE: </strong>Understanding how to predict appropriate uptake of adult-oriented medical care is important for adult patients with pediatric-onset chronic health conditions with continued health vulnerability. We examined associates of engagement in adult survivors of childhood cancer following transfer to adult-oriented care.</p>

<p><strong>METHODS: </strong>Adult survivors of childhood cancer (N&nbsp;= 80), within 1-5&nbsp;years post transfer from pediatric to adult-oriented follow-up care, completed assessments of engagement with recommended adult-oriented follow-up care and psychosocial and transition readiness measures. Measures were validated with adolescent and young adults and/or intended to measure readiness to transition to adult care.</p>

<p><strong>RESULTS: </strong>Earlier age at diagnosis, parental involvement in health care decision-making, higher motivation, and increased comfort speaking to providers about health concerns were significantly associated with attendance at adult-oriented follow-up care visits.</p>

<p><strong>CONCLUSIONS: </strong>Associates of engagement in adult care are complex, representing social-ecological variables. Current measures of transition readiness or adolescent and young adult health-related measures may not adequately capture the associates of engagement in care or identify targets of intervention to promote successful transfer of care. Identifying patients at risk for loss to follow-up will be useful to design interventions for young adult survivors of childhood cancer and other young adults with pediatric-onset chronic conditions who require ongoing adult-oriented care.</p>

10.1016/j.jadohealth.2016.08.018

J Adolesc Health

28270337

Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

2016

2016 Jul 5

1527-7755

<p><strong>PURPOSE: </strong>The development of endocrinopathies in survivors of childhood cancer as they age remains understudied. We characterized endocrine outcomes in aging survivors from the Childhood Cancer Survivor Study on the basis of therapeutic exposures.</p>

<p><strong>PATIENTS AND METHODS: </strong>We analyzed self-reported conditions in 14,290 5-year survivors from the Childhood Cancer Survivor Study, with a median age 6 years (range, &lt; 1 to 20 years) at diagnosis and 32 years (range, 5 to 58 years) at last follow-up. Identification of high-risk therapeutic exposures was adopted from the Children's Oncology Group Long-Term Follow-Up Guidelines. Cumulative incidence curves and prevalence estimates quantified and regression models compared risks of primary hypothyroidism, hyperthyroidism, thyroid neoplasms, hypopituitarism, obesity, diabetes mellitus, or gonadal dysfunction between survivors and siblings.</p>

<p><strong>RESULTS: </strong>The cumulative incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors (P &lt; .01 for all). Risk was significantly higher in survivors exposed to high-risk therapies compared with survivors not so exposed for primary hypothyroidism (hazard ratio [HR], 6.6; 95% CI, 5.6 to 7.8), hyperthyroidism (HR, 1.8; 95% CI, 1.2 to 2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2 to 7.5), thyroid cancer (HR, 9.2; 95% CI, 6.2 to 13.7), growth hormone deficiency (HR, 5.3; 95% CI, 4.3 to 6.4), obesity (relative risk, 1.8; 95% CI, 1.7 to 2.0), and diabetes mellitus (relative risk, 1.9; 95% CI, 1.6 to 2.4). Women exposed to high-risk therapies had six-fold increased risk for premature ovarian insufficiency (P &lt; .001), and men demonstrated higher prevalence of testosterone replacement (P &lt; .001) after cyclophosphamide equivalent dose of 20 g/m(2) or greater or testicular irradiation with 20 Gy or greater. Survivors demonstrated an increased risk for all thyroid disorders and diabetes mellitus regardless of treatment exposures compared with siblings (P &lt; .001 for all).</p>

<p><strong>CONCLUSION: </strong>Endocrinopathies in survivors increased substantially over time, underscoring the need for lifelong subspecialty follow-up of those at risk.</p>

10.1200/JCO.2016.66.6545

J. Clin. Oncol.

27382091

Engagement and experience with cancer-related follow-up care among young adult survivors of childhood cancer after transfer to adult care.

2016

342-50

2016 Apr

1932-2267

<p><strong>PURPOSE: </strong>Young adult survivors (YAS) of childhood cancer require annual adult-focused, cancer-related follow-up given their risk for late effects of treatment. This study describes perception of and engagement with adult-focused, cancer-related follow-up care and general health care among YAS formally transferred to adult care from pediatric survivorship care.</p>

<p><strong>METHODS: </strong>YAS transferred from pediatric survivorship care in the prior 1-5&nbsp;years completed measures indicating engagement with cancer-related follow-up care, other health care utilization, content of communication by providers, quality of cancer-related care, and satisfaction with health care in the prior year.</p>

<p><strong>RESULTS: </strong>Eighty YAS (M age = 27.7&nbsp;years, M time since diagnosis = 10.4&nbsp;years) participated. Just over half of YAS surveyed (n = 44, 55&nbsp;%) endorsed continuing cancer-related follow-up care since transfer. Those with cancer-related follow-up endorsed seeing subspecialty survivorship providers (n = 16, 44&nbsp;%) and primary care providers (n = 22, 50&nbsp;%) or utilizing a shared care model (n = 6, 14&nbsp;%). About a third of YAS endorsed seeing subspecialists (n = 29, 36&nbsp;%) or using other support services (n = 22, 27&nbsp;%). YAS-perceived content of communication varied significantly depending on care model with less cancer-related content being discussed by primary care providers, though perceived quality of cancer-related care and satisfaction with health care was generally favorable.</p>

<p><strong>CONCLUSIONS: </strong>YAS report less than optimal engagement in cancer-related follow-up care and communication in their health care encounters.</p>

<p><strong>IMPLICATIONS FOR CANCER SURVIVORS: </strong>Young adult survivors should receive anticipatory guidance about expectations for delivery and content of adult-focused cancer-related follow-up care.</p>

10.1007/s11764-015-0480-9

J Cancer Surviv

26303367

Histology of Testicular Biopsies Obtained for Experimental Fertility Preservation Protocol in Boys with Cancer.

2015

1420-4

2015 Nov

1527-3792

<p><strong>PURPOSE: </strong>Cryopreservation of testicular tissue with subsequent reimplantation after therapy has the potential to preserve fertility for prepubertal boys with cancer. We present the histology and feasibility of testicular tissue procurement for this novel approach.</p>

<p><strong>MATERIALS AND METHODS: </strong>We performed a prospective cohort study of boys at significant risk for treatment associated gonadotoxicity who were eligible for an experimental research protocol between 2008 and 2011. Open testicular biopsy was performed while the patients were anesthetized for another treatment related procedure. Half of the specimen was reserved for cryopreservation, while the other half was used for research purposes. Semithin sections of the biopsy specimens were evaluated for histological features and compared to age adjusted reference values.</p>

<p><strong>RESULTS: </strong>A total of 34 boys underwent biopsy between March 2008 and October 2011. Of the patients 29 had solid tumors and 5 underwent hematopoietic stem cell transplantation for benign disease. A total of 27 patients had adequate tissue for histological analysis. Median patient age was 8.7 years (IQR 2.2 to 11.5). All children had either normal (81.5% of patients) or increased (18.5%) numbers of germ cells per tubule for their age. However, 5 of 26 patients (19%) older than 6&nbsp;months had no evidence of adult dark spermatogonia and 9 of 16 (56%) older than 6 years had no evidence of primary spermatocytes on biopsy, which would be expected based on age norms. These findings are suggestive of abnormal germ cell maturation.</p>

<p><strong>CONCLUSIONS: </strong>The preliminary histological findings of abnormal spermatogenesis maturation in the testes of prepubertal boys with cancer warrants further investigation.</p>

10.1016/j.juro.2015.04.117

J. Urol.

26032139