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.

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.

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.

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.

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.

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.

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.

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.

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on treatment and management considerations for 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 AYA Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

Fertility perspectives and priorities among male adolescents and young adults in cancer survivorship.

Infertility is a common and distressing late effect of cancer treatment among male survivors. Investigators examined desire for parenthood, prioritization of fertility compared to other life goals, and reports of fertility-related discussions among a cohort of male adolescent and young adult survivors. Eighty percent desired a biological child, yet only 31% ranked having a child among their "top 3" life goals. Only 40% reported fertility-related discussions with their health care providers in survivorship. Given the importance of biological children among this cohort, future guidelines should encourage a more proactive approach to providing fertility counseling and offering testing, to mitigate distress and prevent unplanned pregnancies.

Rhabdomyosarcoma of the Breast in Adolescent and Young Adult (AYA) Women.

Soft tissue sarcoma constitutes 8% of all tumors in adolescent and young adults (AYA), with rhabdomyosarcoma (RMS) accounting for 5.2% to 6.5% of the soft tissue sarcoma total within this group. AYAs have a higher propensity for metastasis and inferior outcomes. Metastases to the breast have been reported in ∼3% to 6% of RMS cases. A review of our hospital's tumor registry identified cases of RMS diagnosed between January 1, 2004 and December 31, 2013. A total of 46 patients with RMS were identified, having a mean age of 12.5 years (range, 1 to 49 y). There were 26 males (57%) and 20 females (43%). Eighteen patients (39%) were AYAs, including 10 women. Four patients (8.7%) were identified with breast involvement, all of whom were AYA females. Treatment modalities included chemotherapy, surgical resection, and radiation. One patient is a long-term survivor. Although RMS is uncommon in AYAs, breast involvement occurs almost exclusively in AYA women and is associated with alveolar histology, metastatic disease, and poor outcomes. In total, 4/10 of all AYA females had breast involvement. Routine examination or imaging of the breasts in AYAs with RMS is not currently standard practice at diagnosis or follow-up, but this analysis suggests it should be considered in female AYA patients.

Pulmonary Nodule Size <5 mm Still Warrants Investigation in Patients With Osteosarcoma and Ewing Sarcoma.

BACKGROUND: Osteosarcoma (OS) and Ewing sarcoma (ES) have a high propensity to develop pulmonary metastases. Lung lesions with calcification, peripheral location, and size >5 mm are more likely to represent malignant metastases. We evaluated the incidence of malignancy in nodules 5 mm or less to potentially guide decisions between biopsy and observation. MATERIALS AND METHODS: A retrospective review of patients <25 years of age with metastatic OS and ES treated at our institution between 2001 and 2014 who had undergone pulmonary nodule biopsy was performed. Computed tomographic scans were reviewed to evaluate nodule size and change over time. RESULTS: Thirty-five patients (27 OS, 8 ES) met inclusion criteria. One hundred sixteen nodules were biopsied (97 OS, 19 ES). Nodule size at biopsy was not significantly different between the malignant (median, 6 mm, range, 1 to 79 mm) and benign (median, 3 mm, range, 1 to 21 mm) lesions (P=0.063). Size of pulmonary nodules <5 mm was not entirely predictive of benign status, with sensitivity estimate of 0.709 (95% confidence interval, 0.465-0.872; P=0.091) and specificity estimate of 0.776 (95% confidence interval, 0.324-0.962; P=0.219) for all nodules biopsied. CONCLUSIONS: Pulmonary nodules in patients with OS and ES <5 mm cannot be excluded from biopsy considerations.

Hypoxic Proliferation of Osteosarcoma Cells Depends on Arginase II.

BACKGROUND/AIMS: Despite significant advancements in the diagnosis and treatment of osteosarcoma, the overall survival has remained relatively unchanged for over two decades. Hypoxic conditions have been demonstrated in solid tumors and are associated with increased cell proliferation and angiogenesis. L-arginine metabolism by arginase produces L-ornithine, the precursor for polyamine and proline synthesis required for cellular proliferation. We hypothesized that hypoxia would increase cellular proliferation via arginase induction in human osteosarcoma cell lines. METHODS: We utilized a variety of approaches to examine the role of arginase II in hypoxic (1% O2, 5% CO2) cellular proliferation. RESULTS: Arginase II mRNA and protein levels were significantly increased in osteosarcoma cells exposed to hypoxia for 48 hours. There were twice as many viable cells following 48 hours of hypoxia than following 48 hours of normoxia (21% O2, 5% CO2). The addition of difluoromethylornithine (DFMO), a putative arginase inhibitor, prevented hypoxia-induced proliferation. Transfection of small interfering RNAs (siRNA) targeting arginase II resulted in knockdown of arginase II protein levels and prevented hypoxia-induced cellular proliferation. CONCLUSIONS: These data support our hypothesis that hypoxia increases proliferation of osteosarcoma cells in an arginase II-dependent manner. We speculate that arginase II may represent a therapeutic target in osteosarcoma.

Adolescent and Young Adult (AYA) Oncology in the United States: A Specialty in Its Late Adolescence.

Over the last 30 years, it has become apparent that oncology patients ages 15 to 39 have not reaped the same rewards of improved survival that we have seen in younger and older patients. As a result, in 2006 the Adolescent and Young Adult (AYA) Oncology Progress Review Group convened and examined the factors that impact the care of the 70,000 new cases per year (approximately 7% of all new cases) in the United States and published their findings. The reasons for inferior survival gains are of course multiple and include the settings in which patients are cared for, clinical trial enrollment, insurance coverage, varied treatment of sarcomas, varied treatment of acute lymphoblastic leukemia, the psychosocial impact of cancer and cancer survivorship. A new area of a yet-to-be completely defined subspecialty was born out of this meeting: AYA oncology. As a medical community we realized that these patients do not fit neatly into the pediatric nor adult world and, therefore, require a unique approach which many individuals, oncology centers, advocacy groups, and cooperative trial groups have started to address. This group of dedicated providers and advocates has made strides but there is still much work to be done on the local, national, and international level to make up for shortcomings in the medical system and improve outcomes. We review key components of AYA cancer care in 2015 that all providers should be aware of, how far we have come, where this movement is headed, and the obstacles that continue to stand in the way of better cure rates and quality of life after cure for this unique group of patients. Like an adolescent maturing into adulthood, this movement has learned from the past and is focused on moving into the future to achieve its goals.

εGγAγδß0-thalassemia: a rare but clinically significant cause of hemolytic anemia in infants.

Normal hemoglobin is made of a tetramer of 2 α-globin and 2 ß-globin polypeptide chains. Deletions in the ß-globin gene cluster can range from a few hundred base pairs to loss of the entire cluster resulting in rare, but clinically significant, thalassemias. One such entity is εGγAγδß0-thalassemia, a condition that presents within the first few weeks of life as a Coombs-negative hemolytic anemia and is not identified on routine newborn screening or hemoglobin electrophoresis.

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.