Piloting a Patient-Driven Online Survey to Better Understand Cancer in Adolescents and Young Adults (AYA) in the United States.

Adolescents and young adults (AYAs) with cancer are a unique patient population in oncology. An opt-in, secure online survey was conducted among a general population of AYA patients and survivors to better understand the current landscape of AYA cancer. A 28-item online survey was designed for cancer patients and survivors diagnosed between the ages of 18 and 39 years. It comprised questions about demographics, treatment site, clinical trial involvement, support services available, and impact on employment, schooling, and finances. A total of 590 patients registered and 447 (76%) completed the survey. This online exercise was found to be feasible and can serve as an effective method to survey the AYA cancer population.

Disease Control and Toxicity Outcomes after Stereotactic Ablative Radiation Therapy for Recurrent and/or Metastatic Cancers in Young-Adult and Pediatric Patients.

BACKGROUND: Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population. METHODS: This was a single-institutional study in patients < 30 years treated with SABR. The primary endpoint was local control (LC), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. The survival analysis was performed using Kaplan-Meier estimates in R v4.2.3. RESULTS: In total, 48 patients receiving 135 SABR courses were included. The median age was 15.6 years (interquartile range, IQR 14-23 y) and the median follow-up was 18.1 months (IQR: 7.7-29.1). The median SABR dose was 30 Gy (IQR 25-35 Gy). The most common primary histologies were Ewing sarcoma (25%), rhabdomyosarcoma (17%), osteosarcoma (13%), and central nervous system (CNS) gliomas (13%). Furthermore, 57% of patients had oligometastatic disease (≤5 lesions) at the time of SABR. The one-year LC, PFS, and OS rates were 94%, 22%, and 70%, respectively. No grade 4 or higher toxicities were observed, while the rates of any grade 1, 2, and 3 toxicities were 11.8%, 3.7%, and 4.4%, respectively. Patients with oligometastatic disease, lung, or brain metastases and those who underwent surgery for a metastatic site had a significantly longer PFS. LC at 1-year was significantly higher for patients with a sarcoma histology (95.7% vs. 86.5%, p = 0.01) and for those who received a biological equivalent dose (BED10) > 48 Gy (100% vs. 91.2%, p = 0.001). CONCLUSIONS: SABR is well tolerated in pediatric patients with 1-year local failure and OS rates of <10% and 70%, respectively. Future studies evaluating SABR in combination with systemic therapy are needed to address progression outside of the irradiated field.

Adolescent and Young Adult (AYA) Oncology, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on considerations for the comprehensive care of AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

Constipation and GI diagnoses in children with solid tumours: prevalence and management.

OBJECTIVES: Despite continued development of targeted therapies for children with cancer, patients continue to experience an array of unwanted side effects. Children with solid tumours may experience constipation as a result of vinca alkaloid therapy, psychological stressors, periods of inactivity and opioid use. Our objective was to investigate the prevalence and treatment of constipation in hospitalised children with solid tumours treated with chemotherapy. METHODS: We retrospectively analysed data from 48 children's hospitals in the Pediatric Health Information System, extracting patients 0-21 years of age with a solid tumour diagnosis hospitalised from October 2015 through December 2019. RESULTS: We identified 13 375 unique patients with a solid tumour diagnosis receiving chemotherapy. Constipation was the most common gastrointestinal complaint with 8658 (64.7%; 95% Cl: 63.9% to 65.5%) having a constipation diagnosis or having received at least two laxatives during admission. Bone cancers had the highest percentage (69.9%) of patients with constipation, while Hodgkin's lymphoma had the lowest, although 52.1% of patients were affected. A total of 44% (n=35 301) of encounters received an opioid at some point during admission. Of patients receiving constipation medications, the most commonly prescribed was polyethyl glycol (n=25 175, 31.7%), followed by docusate (n=11 297, 14.2%), senna (n=10 325, 13.0%) and lactulose (n=5501, 6.9%). CONCLUSIONS: Constipation is the most common gastrointestinal issue that children with solid tumours experience while receiving chemotherapy in the inpatient setting. Increased attention should be given to constipation prophylaxis and treatment in children with solid tumours undergoing chemotherapy, particularly those identified as high risk.

The impact of hiring a full-time fertility navigator on fertility-related care and fertility preservation at a pediatric institution.

Fertility navigators (FNs) are important in communicating infertility risk and fertility preservation (FP) options to patients receiving gonadotoxic therapies. This retrospective study examined electronic medical records of patients with fertility consults at a large pediatric institution (2017-2019), before and after hiring a full-time FN. Of 738 patient encounters, 173 consults were performed pre-navigator and 565 post-navigator. Fertility consults for long-term follow-up cancer survivors increased most substantially: pre-navigator (n = 7) and post-navigator (n = 387). Across diagnoses, females had a larger increase in consults compared to males (χ2 [3, N = 738] = 8.17, p < .05). Findings highlight FNs' impact on counseling rates, particularly in survivorship.

Clinical outcomes and efficacy of stereotactic body radiation therapy in children, adolescents, and young adults with metastatic solid tumors.

OBJECTIVE: The objective of this study is to report disease outcomes and toxicity with the use of stereotactic body radiation therapy (SBRT) in the treatment of pediatric metastatic disease. METHODS: All pediatric and adolescent young adult (AYA) patients' who received SBRT were included between the years 2000 and 2020. Study endpoints included local control (LC), progression-free survival (PFS), overall survival (OS), cumulative incidence (CI) of death or local failure and toxicity. The end points with respect to survival and LC were calculated using the Kaplan-Meier estimate. The cumulative incidence of local failure was calculated using death as a competing risk. RESULTS: 16 patients with 36 lesions irradiated met inclusion criteria and formed the study cohort. The median OS and PFS for the entire cohort were 17 months and 15.7 months, respectively. The 1 year OS for the entire cohort was 75%. The 6- and 12 month local control was 85 and 78%, respectively. There were no local failures in irradiated lesions for patients who received a BED10≥100 Gy. Patients who were treated with SBRT who had ≤5 metastatic lesions at first recurrence had a superior 1 year OS of 100 vs 50% for those with >5 lesions. One patient (6.3%) experienced a Grade 3 central nervous system toxicity. CONCLUSION: LC was excellent with SBRT delivered to metastatic disease, particularly for lesions receiving a BED10≥100 Gy. High-grade toxicity was rare in our patient population. Patients with five or fewer metastatic sites have a significantly better OS compared to >5 sites. ADVANCES IN KNOWLEDGE: This study demonstrates that SBRT is safe and efficacious in the treatment of pediatric oligometastatic disease.

Malnutrition identification and management variability: An administrative database study of children with solid tumors.

BACKGROUND: Malnutrition during cancer treatment increases treatment-related morbidity and mortality. Our study better characterizes variability in malnutrition identification and treatment by examining nutrition-related diagnoses and support for children with central nervous system (CNS) and non-CNS solid tumors during therapy. We examined diagnosis of malnutrition, use of tube feeding or parenteral nutrition (PN), and appetite stimulants. METHODS: We retrospectively reviewed 0 to 21-year-old patients in the Pediatric Health Information System from 2015 to 2019. Patients were classified as having (1) billed malnutrition diagnosis, (2) malnutrition diagnosis or using PN and enteral nutrition ("functional malnutrition"), and (3) any previous criteria or prescribed appetite stimulants ("possible malnutrition"), as well as associated risk factors. RESULTS: Among 13,375 unique patients, CNS tumors were most common (24.4%). Overall, 26.5% of patients had malnutrition diagnoses, 45.4% met functional malnutrition criteria, and 56.0% had possible malnutrition. Patients with adrenal tumors had highest billed, functional, and possible malnutrition (36.6%, 64.1%, and 69.4%, respectively) followed by CNS tumors (29.1%, 52.4%, and 64.1%). Patients with adrenal tumors had highest rates of PN use (47.4%) and those with CNS tumors had the highest tube feeding use (26.8%). Hospital admissions with malnutrition had a longer hospital length of stay (LOS) (6 vs 3 days, P < 0.0001), more emergency department admissions (24.4% vs 21.8%, P < 0.0001), and more opioid use (58.6% vs 41.4%, P < 0.0001). CONCLUSIONS: Variability in malnutrition diagnoses hinders clinical care and nutrition research in pediatric oncology. Improving disease-specific recognition and treatment of malnutrition can target nutrition support, ensure appropriate reimbursement, and potentially improve outcomes for children with solid tumors.

Targeted Therapy in a Young Adult With a Novel Epithelioid Tumor Driven by a PRRC2B-ALK Fusion.

This case report describes an 18-year-old woman with an unusual epithelioid tumor of the omentum with a novel PRRC2B-ALK fusion. Although the atypical pathologic features raised significant diagnostic challenges, expression of CD30 on tumor cells and detection of an ALK rearrangement provided critical information for selecting targeted therapy in a patient not suitable for surgical resection. Despite an initially promising therapeutic response, the patient died. The efficacy of treatment was confirmed by the lack of viable tumor cells at autopsy. This case highlights the role of timely targeted therapy in patients with rare tumors and novel actionable molecular targets.

Parent-Adolescent Concordance Regarding Fertility Perspectives and Sperm Banking Attempts in Adolescent Males With Cancer.

OBJECTIVE: Approximately half of male childhood cancer survivors experience impaired fertility, yet fertility preservation (FP) remains underutilized. Although parent recommendation influences adolescents' decision-making, parents may be uncertain and/or underrate their sons' parenthood goals. This study assessed parent-adolescent and family-level concordance regarding adolescent fertility perspectives (i.e., values, goals) and associations with FP attempts. METHODS: A prospective pilot study examined the impact of a family-centered values clarification tool (FAST) on banking attempts among adolescent males newly diagnosed with cancer at risk for infertility. The FAST assessed adolescent and parent perceptions of adolescents' fertility values and goals (i.e., perceived threat of infertility, perceived benefits/barriers to banking). Parent-adolescent concordance and family-level concordance on fertility perspectives were examined, along with associations with banking attempts and salient demographic factors. RESULTS: Ninety-eight participants (32 adolescents aged 12-20, 37 mothers, 29 fathers) from 32 families completed the FAST before treatment initiation. Parent-adolescent dyads were concordant on approximately one-half of responses. Banking attempts were associated with higher family-level concordance regarding perceived benefits, r(32) = .40, p = .02. Older adolescent age was associated with higher family-level concordance regarding perceived threat, r(31) = .37, p = .04, and benefits, r(32) = .40, p = .03. Fathers' education was associated with higher family-level concordance regarding barriers, r(21) = .53, p = .01. CONCLUSIONS: When parents were concordant with their son's fertility values and goals, particularly perceived benefits, adolescents were more likely to attempt FP. Clinicians should facilitate sharing of fertility perspectives within families before cancer treatment, especially with younger adolescents. Psychosocial support for families facing FP decisions is recommended at diagnosis and across the care continuum.

Satisfaction with Fertility Preservation Decisions among Adolescent Males with Cancer: A Mixed Methods Study.

Half of male childhood cancer survivors experience treatment-related fertility impairment, which can lead to distress. Survivors often regret forgoing fertility preservation (FP), and decisional dissatisfaction is associated with a lower quality of life. This mixed methods study examined short-term FP decisional satisfaction among families of male adolescents newly diagnosed with cancer who received an initial fertility consult and completed an FP values clarification tool. One-two months after the FP decision, thirty-nine families completed the Brief Subjective Decision Quality measure. Decisional satisfaction was compared for participants (mothers, fathers, adolescents) who did and did not attempt to bank. Semi-structured interviews included the following question: How do you/your family feel about the banking decision now/in the future? Decisional quality scores were moderate-high (M = 5.74-6.33 out of 7), with no significant differences between non-attempter (n = 15) and attempter (n = 24) families (adolescents: p = 0.83, d = 0.08; mothers: p = 0.18, d = 0.45; fathers: p = 0.32, d = 0.44). Three qualitative themes emerged among non-attempter families: (1) satisfaction with decision (50% of participants), (2) acceptance of decision (60%), and (3) potential for future regret (40%). Satisfaction with decision was the only theme identified in attempter families (93%). Quantitively, short-term decisional satisfaction was high regardless of the banking attempt. However, the qualitative findings suggest that the experiences of families who did not bank may be more nuanced, as several participants discussed a potential for future regret, highlighting the importance of ongoing support.

Impact of a novel family-centered values clarification tool on adolescent sperm banking attempts at the time of a new cancer diagnosis.

PURPOSE: Over half of males experience fertility impairment after childhood cancer therapy, which often causes psychosocial distress. Yet, fertility preservation (FP) remains underutilized. The goals of this study were to determine the feasibility and impact of implementing a family-centered FP values clarification tool on sperm banking attempts among adolescent males newly diagnosed with cancer, and identify key determinants of banking attempts. METHODS: A prospective pilot study was conducted among families of males (12-25 years old), prior to cancer therapy. Thirty-nine of 41 families agreed to participate (95%); 98 participants (32 adolescents, 37 mothers, 29 fathers) completed the Family-centered Adolescent Sperm banking values clarification Tool (FAST). Analyses assessed the impact of the FAST on banking attempts and examined associations between demographic/medical characteristics, FAST subscales (perceived threat, benefits, barriers), and banking attempts. RESULTS: Twenty-three (59%) adolescents attempted to bank, compared to 8 adolescents (33%) during baseline assessment (p=.04). Significant associations were identified between banking attempts and adolescents' report of perceived threat (rpb=.45, p=.01) and benefits (rpb=.57, p=.01). Only mothers' proxy reports of adolescent perceived threat (rpb=.42, p=.01) and benefits (rpb=.47, p=.003) were associated with banking attempts, while fathers' self-reported perceived benefits (rpb=.43, p=.03), self-reported barriers (rpb=.49, p=.01), and proxy reports of adolescent perceived threat (rpb=.38, p=.04) and benefits (rpb=.59, p=.02) were associated with banking attempts. CONCLUSION: Adolescent sperm banking attempt rates significantly increased after implementation of a family-centered FP values clarification tool prior to cancer treatment. Findings underscore the importance of targeting both adolescents and their parents, particularly fathers, in FP efforts.

Evaluating Perspectives of a Smartphone Medication Application in the Adolescent and Young Adult Oncology Population: A Qualitative Study.

Purpose: Medication adherence research involving adolescent and young adult (AYA) oncology patients has consisted of small, retrospective studies demonstrating poor adherence rates. Technology plays an active role in attempt to improve medication adherence. There is a growing body of literature investigating the role of smartphone applications (apps). We hypothesized a medication phone app, MedActionPlan Pro (MPP), leads to perceived improvement in medication adherence. Methods: Thirty AYA oncology patients actively receiving treatment (AYA defined as 15-30 years) at Nationwide Children's Hospital were enrolled. Participants downloaded the MPP app on their smartphone for 3 months, during which time participants were provided text messages and alerts to encourage medication adherence. Post-app use, participants completed semi-structured interviews. Interviews were audio-recorded, transcribed, and independently coded to determine consensus thematic content. Results: Thirty AYA oncology participants (16 male), median age 17.5 (range: 15-30 years), participated in the study, with 22 participants (55% male) with a median age of 18 years (range: 15-30 years) participated in the final qualitative survey interview. Participants reported positive views about app utilization and perceived improved medication adherence. Additional themes included perceived decreased forgetfulness, improved organization, and identified customization for medications within the app was most important to AYAs. Conclusion: AYA oncology patients reported improvement in perceived medication adherence utilizing MPP and identified several features they thought would lead to improved medication adherence. These findings, integrated with previous literature, support the further need to investigate the utility of medication adherence apps that fit the unique needs of AYA oncology patients.

Evaluating Age-related Disparity of Outcomes in Ewing Sarcoma Patients Treated at a Pediatric Academic Medical Center.

Adolescent and young adult (AYA) patients with Ewing sarcoma have inferior survival compared with pediatric patients even when treated with similar regimens. Investigation into specific explanations is lacking. A retrospective chart review of Ewing sarcoma patients at a single institution was performed, and 104 patients were identified, 45 were 15 to 39 years of age (AYA cohort) and 59 younger than 15 years (pediatric cohort). AYA patients demonstrated more metastatic disease (50% vs. 24%, P=0.009), peripheral tumor location (64% vs. 41%, P=0.025), percentage of male patients (76% vs. 51%; P=0.010), and tumor size ≥5 cm (93% vs. 70%, P=0.016) than pediatric patients. Five-year overall survival was 77.7% and 53.0% and event-free survival was 68.7% and 40.6% for pediatric versus AYA, respectively. Similar rates of toxicity and chemotherapeutic dose adjustments were demonstrated. In this cohort, increased AYA patient mortality appears to be related to disease characteristics rather than treatment-related differences.

Low toxicity and favorable overall survival in relapsed/refractory B-ALL following CAR T cells and CD34-selected T-cell depleted allogeneic hematopoietic cell transplant.

To define the tolerability and outcome of allogeneic hematopoietic stem cell transplant (allo-HSCT) following CAR T-cell therapy, we retrospectively reviewed pediatric/young adult patients with relapsed/refractory B-ALL who underwent this treatment. Fifteen patients (median age 13 years; range 1-20 years) with a median potential follow-up of 39 months demonstrated 24-month cumulative incidence of relapse, cumulative incidence of TRM, and OS of 16% (95% CI: 0-37%), 20% (95% CI: 0-40%), and 80% (95% CI: 60-100%), respectively. Severe toxicity following CAR T cells did not impact OS (p = 0.27), while greater time from CAR T cells to allo-HSCT (>80 days) was associated with a decrease in OS. In comparing CD34-selected T-cell depleted (TCD; n = 9) vs unmodified (n = 6) allo-HSCT, the cumulative incidence of relapse, TRM, and OS at 24 months was 22% (95% CI: 0-49%) vs 0% (p = 0.14), 0% vs 50% [95% CI: 10-90%] (p = 0.02) and 100% vs 50% [95% CI: 10-90%] (p = 0.02). In this small cohort of patients, CAR T cells followed by a CD34-selected TCD allo-HSCT appears to result in less TRM and favorable OS when compared with unmodified allo-HSCT. There was no evidence that disease control was impacted by the type of consolidative allo-HSCT, which demonstrates the feasibility of this approach.

Ocular hemorrhage secondary to thioguanine-associated veno-occlusive disease in a child with acute lymphoblastic leukemia in delayed intensification.

Hepatic VOD is a potentially fatal complication during stem cell transplantation and is rarely seen in the non-transplant setting. We report the case of a five-year-old boy who presented with visual complaints during delayed intensification phase of treatment for ALL. He was found to have bilateral retinal hemorrhages associated with profound thrombocytopenia due to chemotherapy. VOD was diagnosed based on EBMT criteria and was managed with supportive care. Despite resolution of VOD, his vision progressively deteriorated and resulted in blindness. This case highlights the significance of close monitoring of ALL patients in delayed intensification when they are at risk for developing VOD, the importance of refractory thrombocytopenia as a diagnostic feature and the potential for VOD to manifest with intraocular bleeding.

Two Successful Sperm Aspirations in High-Risk Adolescent and Young Adult Lymphoma Patients Before Initiation of Emergent Therapy.

As survival rates for adolescent and young adult (AYA) cancer patients improve, fertility preservation has gained increased attention. Many AYAs report significant concerns about fertility potential after therapy. Preservation at diagnosis may be the only opportunity for future genetic parenthood for many patients. Time constraints, concerns about treatment delays, and difficulty accessing resources are reported as reasons for providers not providing counseling. In addition, some pubertal males are unable/unwilling to produce a sample through self-stimulation. Testicular sperm aspiration/extraction with sperm cryopreservation can be successfully performed in "high-risk" pubertal males with significant barriers to traditional collection before initiation of emergent chemotherapy.

First-in-Human Intravenous Seprehvir in Young Cancer Patients: A Phase 1 Clinical Trial.

Seprehvir (HSV1716) is an oncolytic herpes simplex virus-1 (HSV-1) previously demonstrated to be well tolerated in pediatric patients when administered intratumorally. To determine the safety of administering Seprehvir systemically, we conducted the first-in-human phase I trial of intravenous injection in young patients with relapsed or refractory extra-cranial solid cancers. We delivered a single dose of 5 × 104 infectious units (iu)/kg (maximum dose of 2 × 106) or 2.5 × 105 iu/kg (maximum dose of 1 × 107 iu) of Seprehvir via the peripheral vein, monitored adverse events, and measured tumor responses by imaging. We monitored HSV-1 serology as well as viremia and shedding by PCR and culture. We administered a single dose of Seprehvir to seven patients and multiple doses to two patients. We did not observe any dose-limiting toxicities. All five HSV-1 seronegative patients seroconverted by day 28. Four of nine patients had detectable HSV-1 genomes in peripheral blood appearing on day +4 consistent with de novo virus replication. Two patients had stable disease in response to Seprehvir. Intravenous Seprehvir is well tolerated without viral shedding in children and young adults with late-stage cancer. Viremia consistent with virus replication holds promise for future Seprehvir studies at higher doses and/or in combination with other anti-neoplastic therapies.

Perceptions of participating in family-centered fertility research among adolescent and young adult males newly diagnosed with cancer: A qualitative study.

BACKGROUND: Over half of male childhood cancer survivors experience infertility after treatment, which is known to cause distress and impact future quality of life. Sperm banking rates remain low, and little is known about how adolescent and young adult (AYA) males and their families make fertility preservation (FP) decisions. This study examined AYA and parent perceptions of participating in a research study focused on testing a new FP decision tool at the time of cancer diagnosis. METHODS: Forty-four participants (19 mothers, 11 fathers, 14 male AYAs 12-25 years old) from 20 families completed brief assessments at diagnosis and approximately one month later, including a qualitative interview exploring the impact of study participation. Verbatim transcripts were coded through thematic content analysis using the constant comparison method. RESULTS: Two major themes emerged: (1) a positive effect of participating in the study and (2) a neutral effect (no positive/negative effect of participation). Subthemes that emerged for participants who noted a positive effect included (a) participation prompted deeper thinking, (b) participation influenced family conversations, and (c) participation resulted in altruism/helping others. No participant reported a negative effect. CONCLUSIONS: This study demonstrates that participation in family-centered research focused on FP among AYA males, before treatment begins, is perceived as beneficial or neutral at the time of a new cancer diagnosis. These findings provide support for future family-centered FP interventions for this population.

Conducting reproductive research during a new childhood cancer diagnosis: ethical considerations and impact on participants.

PURPOSE: Research among adults shows benefits and low perceived burden of engaging in behavioral research. However, questions remain regarding the ethics of conducting behavioral research in pediatric populations during sensitive situations, including during a new life-threatening diagnosis or at end-of-life. We examined reactions to participating in a behavioral reproductive research study among male adolescents newly diagnosed with cancer and their parents, as a step towards optimizing fertility preservation utilization in a population where future infertility is common. METHODS: Pediatric literature regarding the ethics of behavioral research was reviewed. In our pilot, forty-four participants (19 mothers, 11 fathers, 14 male adolescents newly diagnosed with cancer) from 20 families completed demographic questionnaires and a fertility preservation decision tool developed by the study team. Qualitative interviews exploring the impact of study participation were subsequently conducted. Verbatim transcripts were coded for thematic content using the constant comparison method. RESULTS: Literature review showed positive reactions to research participation among youth/caregivers. In our pilot study, 89% (n = 17) of mothers, 64% (n = 7) of fathers, and 71% (n = 10) of adolescents reported at least one benefit of participating. Eleven percent (n = 2) of mothers, 36% (n = 4) of fathers, and 29% (n = 4) of adolescents said they were not affected; none of the participants reported a negative effect. CONCLUSION: Consistent with prior literature, our study suggests behavioral reproductive research prior to cancer treatment can offer direct benefits to participants and society, without increasing burden. These findings will inform future interventions to improve long-term psychosocial and reproductive outcomes for youth with cancer.