Factors Associated With Sun Protection Behaviors Among Childhood Cancer Survivors.

BACKGROUND: Childhood cancer survivors (CCS) are at increased risk of developing skin cancer. Engaging in sun-protective behaviors may ameliorate that risk, but prior work shows that survivors engage in suboptimal levels of sun-protective behaviors. Guided by the Health Belief Model (HBM), this study evaluated factors associated with sun-protective behavior among CCS. METHODS: This is a secondary analysis of a survey study of 94 adult survivors of childhood cancer recruited from a long-term follow-up clinic. Participants reported their sun protection habits, skin type/sensitivity, barriers to sun protection, and perceived severity and susceptibility of getting skin cancer. Descriptive statistics were used to describe the prevalence of sun protection behaviors and hierarchical linear regression was used to evaluate predictors of sun protection behavior following the HBM. RESULTS: On average, CCS engaged in moderate levels of sun-protective behaviors ( M =2.53; SD=0.59). Hierarchical linear regression indicated that fair skin type ( P =0.02) and higher perceived susceptibility relative to noncancer survivors ( P =0.02) were associated with increased sun protection behaviors. Perceived barriers to sun protection were marginally significant ( P =0.09), whereas other constructs from the HBM did not contribute significantly to the model. CONCLUSIONS: Although CCS are at increased risk of developing skin cancer, they engage in suboptimal levels of sun protection behaviors. Findings suggest that interventions to educate survivors about their unique risk of skin cancer and effective prevention behaviors are needed.

Development of a Self-management and Peer-Mentoring Intervention to Improve Transition Readiness Among Young Adult Survivors of Pediatric Cancer: Formative Qualitative Research Study.

BACKGROUND: Childhood cancer survivors require lifelong risk-based follow-up care. It should be noted that less than one-third of adult survivors of childhood cancer report any survivor-focused care, and fewer than 1 in 5 obtain risk-based follow-up care. It is thought that this may be due to inadequate transition readiness, including low levels of knowledge, skills, motivation, and resources to make the transition to independent self-management of follow-up care. Interventions that focus specifically on improving the transition from parent-managed to self-managed care are needed. Theory and prior research suggest that targeting self-management skills and using peer mentoring may be innovative strategies to improve transition readiness. OBJECTIVE: This study aims to identify the content of a self-management intervention to improve transition readiness among adolescent and young adult (AYA) survivors. METHODS: Intervention development occurred in 3 stages: formative research with AYA survivors to identify barriers and facilitators to obtaining risk-based survivorship care, content development using feedback from multiple stakeholders (AYA survivors, parents, and providers), and content refinement (usability testing) of the initial proposed educational modules for the program. Content analysis, guided by the social-ecological model of AYA readiness for transition, was used to identify themes and develop and refine the content for the intervention. RESULTS: A total of 19 AYA survivors participated in the formative research stage, and 10 AYA survivors, parents, and health care providers participated in the content development and refinement stages. The major barrier and facilitator themes identified included knowledge of cancer history and risks; relationships with health care providers; relationships with family members involved in care; emotions about health, follow-up care, and transfer of care; and lifestyle behaviors and life transitions. These themes were translated into 5 self-management modules: understanding treatment history and the survivorship care plan, managing health care logistics and insurance, communicating with health care providers and family members involved in care, dealing with emotions, and staying healthy in the context of life transitions. Feedback from the key stakeholders indicated that the content was relevant but should include participative elements (videos and tailored feedback) to make the intervention more engaging. The AYA survivors were receptive to the idea of working with a peer mentor and expressed a preference for using SMS text messaging, telephone calls, or videoconference to communicate with their mentor. CONCLUSIONS: Incorporating AYA survivors, parents, and providers in the design was essential to developing the content of a self-management and peer-mentoring intervention. AYA survivors confirmed the important targets for the intervention and facilitated design decisions in line with our target users' preferences. The next step will be to conduct a single-arm trial to determine the feasibility and acceptability of the proposed intervention among AYA survivors of childhood cancer.

Genomic landscape of lymphatic malformations: a case series and response to the PI3Kα inhibitor alpelisib in an N-of-1 clinical trial.

Background: Lymphatic malformations (LMs) often pose treatment challenges due to a large size or a critical location that could lead to disfigurement, and there are no standardized treatment approaches for either refractory or unresectable cases. Methods: We examined the genomic landscape of a patient cohort of LMs (n = 30 cases) that underwent comprehensive genomic profiling using a large-panel next-generation sequencing assay. Immunohistochemical analyses were completed in parallel. Results: These LMs had low mutational burden with hotspot PIK3CA mutations (n = 20) and NRAS (n = 5) mutations being most frequent, and mutually exclusive. All LM cases with Kaposi sarcoma-like (kaposiform) histology had NRAS mutations. One index patient presented with subacute abdominal pain and was diagnosed with a large retroperitoneal LM harboring a somatic PIK3CA gain-of-function mutation (H1047R). The patient achieved a rapid and durable radiologic complete response, as defined in RECIST1.1, to the PI3Kα inhibitor alpelisib within the context of a personalized N-of-1 clinical trial (NCT03941782). In translational correlative studies, canonical PI3Kα pathway activation was confirmed by immunohistochemistry and human LM-derived lymphatic endothelial cells carrying an allele with an activating mutation at the same locus were sensitive to alpelisib treatment in vitro, which was demonstrated by a concentration-dependent drop in measurable impedance, an assessment of cell status. Conclusions: Our findings establish that LM patients with conventional or kaposiform histology have distinct, yet targetable, driver mutations. Funding: R.P. and W.A. are supported by awards from the Levy-Longenbaugh Fund. S.G. is supported by awards from the Hugs for Brady Foundation. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of Arizona Cancer Center (CA023074), the University of New Mexico Comprehensive Cancer Center (CA118100), and the Rutgers Cancer Institute of New Jersey (CA072720). B.K.M. was supported by National Science Foundation via Graduate Research Fellowship DGE-1143953. Clinical trial number: NCT03941782.

Feasibility of FitSurvivor: A technology-enhanced group-based fitness intervention for adolescent and young adult survivors of childhood cancer.

BACKGROUND: This study evaluated the feasibility of a technology-enhanced group-based fitness intervention for adolescent and young adult (AYA) survivors of childhood cancer. PROCEDURE: AYA survivors ages 13-25 years were randomized to the intervention (eight in-person group sessions with mobile app and FitBit followed by 4 weeks of app and FitBit only) or waitlist control. Assessments were at 0, 2, 3, 6, and 9 months. Feasibility was evaluated by enrollment, retention, attendance, app engagement, and satisfaction. Secondary outcomes included physical activity, muscular strength/endurance, cardiorespiratory fitness, health-related quality of life, and fatigue. RESULTS: A total of 354 survivors were mailed participation letters; 68 (19%) were screened, of which 56 were eligible and 49 enrolled (88% of those screened eligible, 14% of total potentially eligible). Forty-nine survivors (Mage  = 18.5 years, 49% female) completed baseline assessments and were randomized (25 intervention, 24 waitlist). Thirty-seven (76%) completed the postintervention assessment and 32 (65%) completed the final assessment. On average, participants attended 5.7 of eight sessions (range 1-8). Overall intervention satisfaction was high (M = 4.3, SD = 0.58 on 1-5 scale). Satisfaction with the companion app was moderately high (M = 3.4, SD = 0.97). The intervention group demonstrated significantly greater improvement in lower body muscle strength compared to the waitlist postintervention, and small but not statistically significant changes in other secondary measures. CONCLUSIONS: A group-based intervention with a mobile app and fitness tracker was acceptable but has limited reach due to geographical barriers and competing demands experienced by AYA survivors.

Peppermint Oil: Evaluating Efficacy on Nausea in Patients Receiving Chemotherapy in the Ambulatory Setting.

BACKGROUND: Nausea is one of the most commonly reported side effects in patients receiving chemotherapy. Patients who experience nausea during chemotherapy may also experience depression, metabolic imbalances, dehydration, decreased ability to function, and treatment delays, which can ultimately affect outcomes. OBJECTIVES: This study aimed to determine the efficacy of a cool damp washcloth with peppermint essential oil versus a cool damp washcloth alone on the self-reported intensity of nausea in patients receiving chemotherapy in the outpatient ambulatory setting. METHODS: 79 adult patients receiving chemotherapy were recruited from an outpatient ambulatory infusion center in the southeastern United States. Patients were separated into two groups (no scent and peppermint) and asked to rate the intensity of their chemotherapy-induced nausea at pre- and postintervention using the Baxter Retching Faces pictorial scale. FINDINGS: The results demonstrated that the use of peppermint oil was effective in decreasing the intensity of nausea experienced by patients compared to a cool washcloth alone.

Long-term outcomes for children with acute lymphoblastic leukemia (ALL) treated on The Cancer Institute of New Jersey ALL trial (CINJALL).

The Cancer Institute of New Jersey Acute Lymphoblastic Leukemia trial (CINJALL) employed a post-induction regimen centered on intensive oral antimetabolite therapy, with no intravenous methotrexate (MTX). Fifty-eight patients enrolled between 2001 and 2005. A high rate of induction death (n = 3) or induction failure (n = 1) was observed. Among those who entered remission, five-year DFS is 80 ± 8.9% for those at standard risk of relapse and 76 ± 7.8% for high-risk patients, with median follow up over six years. The estimated cumulative incidence of testicular relapse among boys was elevated (13 ± 7.2%) compared to the rate observed on contemporary protocols. We conclude that post-induction therapy using intensive oral antimetabolites for children with acute lymphoblastic leukemia (ALL) can result in overall long-term DFS comparable to that observed among children treated with regimens including intravenous MTX. However, an increased risk of late extramedullary relapse among boys was observed, supporting the prevailing opinion that high-dose MTX improves outcome for children with ALL.

Skin Cancer Surveillance Behaviors Among Childhood Cancer Survivors.

The risk of developing skin cancer is elevated among childhood cancer survivors (CCS), particularly among those treated with radiation. This survey study examined the skin cancer surveillance behaviors of 94 CCS. Approximately 48% of CCS had ever conducted skin self-examination (SSE) and 31% had ever received a physician skin examination. Rates of physician skin examination were 2.5 times higher among CCS treated with radiation compared to those without radiation. However, rates of SSEs did not differ based on treatment history. These findings highlight the need to promote skin cancer surveillance as an important aspect of CCS survivorship care.

Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial.

The Children's Cancer Group 1952 (CCG-1952) clinical trial studied the substitution of oral 6-thioguanine (TG) for 6-mercaptopurine (MP) and triple intrathecal therapy (ITT) for intrathecal methotrexate (IT-MTX) in the treatment of standard-risk acute lymphoblastic leukemia. After remission induction, 2027 patients were randomized to receive MP (n = 1010) or TG (n = 1017) and IT-MTX (n = 1018) or ITT (n = 1009). The results of the thiopurine comparison are as follows. The estimated 7-year event-free survival (EFS) for subjects randomized to TG was 84.1% (+/- 1.8%) and to MP was 79.0% (+/- 2.1%; P = .004 log rank), although overall survival was 91.9% (+/- 1.4%) and 91.2% (+/- 1.5%), respectively (P = .6 log rank). The TG starting dose was reduced from 60 to 50 mg/m(2) per day after recognition of hepatic veno-occlusive disease (VOD). A total of 257 patients on TG (25%) developed VOD or disproportionate thrombocytopenia and switched to MP. Once portal hypertension occurred, all subjects on TG were changed to MP. The benefit of randomization to TG over MP, as measured by EFS, was evident primarily in boys who began TG at 60 mg/m(2) (relative hazard rate [RHR] 0.65, P = .002). The toxicities of TG preclude its protracted use as given in this study. This study is registered at http://clinicaltrials.gov as NCT00002744.

Primary hemorrhagic stroke in a 12-year-old female with sickle cell disease and normal transcranial Doppler.

Stroke is a well-known complication of sickle cell disease (SCD). It is estimated to occur in approximately 11% of patients with SCD by the age of 20. The most frequent cause of cerebrovascular accident (CVA) is blockage of the intracranial internal carotid and middle cerebral arteries. Hemorrhagic stroke is less common, occurring in approximately 3% of children by age 20. Transcranial Doppler (TCD) is the standard test for prediction of stroke risk in children with sickle cell anemia. The authors present a case of a 12-year-old female with SCD transferred to their institution after suffering a catastrophic intracranial hemorrhage. Her most recent TCD was normal 6 months prior to her admission.

Deep venous thrombosis in adolescents due to anatomic causes.

Aberrant or anomalous anatomy is an under appreciated risk for venous thromboembolic events (VTE). Five adolescents with VTE and predisposing anatomic abnormalities are presented. In three cases, knowledge of the underlying anatomic abnormalities resulted in changes in treatment and management. In two other cases, failure to consider or correct the underlying defect resulted in recurrent thrombosis or post-thrombotic complications. Few case reports are found in the pediatric literature, but a MEDLINE search across all age groups suggests these anomalies are frequently found when appropriate radiological imaging is obtained.

Phase 2B trial of aminopterin in multiagent therapy for children with newly diagnosed acute lymphoblastic leukemia.

PURPOSE: Aminopterin offers advantages over the related antifolate, methotrexate, including greater potency, complete bioavailability, and more consistent accumulation and metabolism by patients' blasts. This current trial was done to document the toxicity of the aminopterin within a multiagent therapeutic regimen for children with newly diagnosed ALL. EXPERIMENTAL DESIGN: Patients at high risk of relapse were non-randomly assigned to therapy including oral aminopterin 4 mg/m(2), in two doses 12 h apart, in place of methotrexate 100 mg/m(2) in four divided doses. RESULTS: Thirty-two patients, 22 with pre-B ALL and ten with T-lineage ALL, have been treated with aminopterin, with median follow up of 40 months. Hematologic, mucosal and hepatic toxicity has been tolerable and reversible. There have been no toxic deaths among patients in remission. During weekly AMT therapy, higher mean neutrophil counts were observed among patients who were wild type for polymorphisms in methylene tetrahydrofolate reductase and methionine synthase reductase. CONCLUSIONS: Aminopterin can be safely incorporated in multiagent therapy for patients with ALL, in place of systemic methotrexate, without causing excessive toxicity. These results support a larger trial comparing the efficacy and toxicity of aminopterin and methotrexate in therapy for patients with ALL.

Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group.

The Children's Cancer Group (CCG) 1952 clinical trial for children with standard-risk acute lymphoblastic leukemia (SR-ALL) compared intrathecal (IT) methotrexate (MTX) with IT triples (ITT) (MTX, cytarabine, and hydrocortisone sodium succinate [HSS]) as presymptomatic central nervous system (CNS) treatment. Following remission induction, 1018 patients were randomized to receive IT MTX and 1009 ITT. Multivariate analysis identified male sex, hepatomegaly, CNS-2 status, and age younger than 2 or older than 6 years as significant predictors of isolated CNS (iCNS) relapse. The 6-year cumulative incidence estimates of iCNS relapse are 3.4% +/- 1.0% for ITT and 5.9% +/- 1.2% for IT MTX; P = .004. Significantly more relapses occurred in bone marrow (BM) and testicles with ITT than IT MTX, particularly among patients with T-cell phenotype or day 14 BM aspirate containing 5% to 25% blasts. Thus, the estimated 6-year event-free survivals (EFS) with ITT or IT MTX are equivalent at 80.7% +/- 1.9% and 82.5% +/- 1.8%, respectively (P = .3). Because the salvage rate after BM relapse is inferior to that after CNS relapse, the 6-year overall survival (OS) for ITT is 90.3% +/- 1.5% versus 94.4% +/- 1.1% for IT MTX (P = .01). It appears that ITT improves presymptomatic CNS treatment but does not improve overall outcome.

Use of a non-traditional university ambulatory practice to teach large animal medicine.

While many other veterinary schools have moved away from a traditional university-based ambulatory practice, the Ohio State University's Large Animal Practice has continued to provide a cost-effective and valuable method of preparing students for today's careers in veterinary medicine. The practice provides a full array of services to production, equine, and camelid clients, including herd health, individual animal medicine and surgery, and emergency services. Acquiring established practices from alumni has formed the client base. Four full-time veterinarians operate the clinic. While these same clinicians do some classroom teaching, their primary responsibility is devoted to the five to six fourth-year veterinary students who rotate through the clinic every two weeks. Teaching methods and objectives for these students include case discussions, homework, truck quiz books, and practice management issues. Financially, the clinic runs as a private practice, with minimal support from the college (201,000 US dollars per fiscal year) and a gross income of 676,000 US dollars per year. Thus, in a cost-effective manner, this required core ambulatory rotation provides students with a scientific learning experience that exposes them to all aspects of large animal production medicine in a real-world setting.

Mitoxantrone and cytarabine induction, high-dose cytarabine, and etoposide intensification for pediatric patients with relapsed or refractory acute myeloid leukemia: Children's Cancer Group Study 2951.

PURPOSE: To evaluate the response rate, survival, and toxicity of mitoxantrone and cytarabine induction, high-dose cytarabine and etoposide intensification, and further consolidation/maintenance therapies, including bone marrow transplantation, in children with relapsed, refractory, or secondary acute myeloid leukemia (AML). To evaluate response to 2-chlorodeoxyadenosine (2-CDA) and etoposide (VP-16) in patients who did not respond to mitoxantrone and cytarabine. PATIENTS AND METHODS: Patients with relapsed/refractory AML (n = 101) and secondary AML (n = 13) were entered. RESULTS: Mitoxantrone and cytarabine induction achieved a remission rate of 76% for relapsed/refractory patients and 77% for patients with secondary AML, with a 3% induction mortality rate. Cytarabine and etoposide intensification exceeded the acceptable toxic death rate of 10%. The response rate of 2-CDA/VP-16 was 8%. Two-year overall survival was estimated at 24% and was better than historical control data. Patients with secondary AML had similar outcomes to relapsed or refractory patients. Initial remission longer than 1 year was the most important prognostic factor for patients with primary AML (2-year survival rate, 75%), whereas for patients with primary AML, with less than 12 months of initial remission, survival was 13% and was similar to that of refractory patients (6%). CONCLUSION: Mitoxantrone and cytarabine induction is effective with reasonable toxicity in patients with relapsed/refractory or secondary AML. The cytarabine and etoposide intensification regimen should be abandoned because of toxicity. Patients with relapsed AML with initial remissions longer than 1 year have a relatively good prognosis.

Cervical spinal cord hemorrhage secondary to neonatal alloimmune thrombocytopenia.

Neonatal alloimmune thrombocytopenia with intracranial hemorrhage is a reported phenomenon. While most of the hemorrhages are noted to be either intraventricular or intraparenchymal, the authors describe the case of a fourth-ventricle hemorrhage with extension into the spinal column down the cervical spinal cord secondary to maternal anti-human platelet antigen (HPA-1a) antibody.