Racialized inequities in live birth after cancer: A population-based study of 63,000 female adolescents and young adults with cancer.

INTRODUCTION: Fertility after cancer is a top concern for adolescents and young adults with cancer (AYAs) (15-39 years old at diagnosis). The authors characterized live births after cancer by race and ethnicity ("race/ethnicity") in a population-based sample of female AYAs. METHODS: This study used Texas Cancer Registry data linked to birth certificates (1995-2016) to estimate cumulative incidence of live birth, based on first live birth after cancer, and compared differences by race/ethnicity. Proportional subdistribution hazards models were used to estimate associations between race/ethnicity and live birth, adjusted for diagnosis age, cancer type, stage, year, and prior live birth, overall and for each cancer type. RESULTS: Among 65,804 AYAs, 10-year cumulative incidence of live birth was lower among non-Hispanic Black AYAs than other racial/ethnic groups: 10.2% (95% confidence interval [CI], 9.4-10.9) compared to 15.9% (95% CI, 14.1-17.9) among Asian or Pacific Islander, 14.7% (95% CI, 14.2-15.3) among Hispanic, and 15.2% (95% CI, 14.8-15.6) among non-Hispanic White AYAs (p < .01). In the adjusted overall model, Black AYAs were less likely to have a live birth after cancer than all other groups. In adjusted models for each cancer type, live birth was significantly less likely for Black AYAs with gynecologic cancers or lymphomas (compared to White AYAs) or thyroid cancers (compared to Hispanic AYAs). CONCLUSION: Black AYAs are less likely than AYAs of other races/ethnicities to have a live birth after cancer, in contrast to patterns of live birth in the general population. Research and action to promote childbearing equity after cancer are imperative.

Response to Pazopanib in Patients With Relapsed Osteosarcoma.

Axial skeleton primary tumor, metastatic disease at presentation, incomplete surgical resection, and <90% tumor necrosis have all been known to influence prognosis adversely in osteosarcoma. Relapse of osteosarcoma, typically occurring within the first 18 months of therapy, with an incidence rate of 50% is treated with surgery, chemotherapy, and targeted therapy. Here, we discuss 2 patients treated with pazopanib, a multi-tyrosine kinase inhibitor presently approved to treat renal cell carcinoma and soft tissue sarcomas. Case 1 achieved positive response and remains on pazopanib. Case 2 sustained gastrointestinal toxicity requiring suspension of drug, despite achieving stable disease.

Models of care for adolescent and young adult cancer programs.

This review draws on the experience of adolescent and young adult (AYA) cancer clinicians from Australia, the United States, and the United Kingdom to summarize common aspects of models of care implemented in their countries. The principles underpinning these models include patient- and family-focused care informed by an understanding of normal AYA development, enhancing existing adult or pediatric cancer services to meet the needs of AYA, and promoting collaboration between pediatric and adult oncologists. Common elements of AYA cancer care include establishing an AYA multidisciplinary team that integrates medical and psychosocial care, efforts to centralize complex care, providing access and equity for all AYA, promoting clinical trials, and helping facilitate transition to healthy survivorship. Several organizational approaches are described, noting that local program development depends on resources, infrastructure, and assessment of unmet needs within the region. The development of national networks provides opportunities for shared learning and approaches to evaluation.

Next steps for adolescent and young adult oncology workshop: An update on progress and recommendations for the future.

Each year, 70,000 adolescents and young adults (AYAs) between ages 15 and 39 years in the United States are diagnosed with cancer. In 2006, a National Cancer Institute (NCI) Progress Review Group (PRG) examined the state of science associated with cancer among AYAs. To assess the impact of the PRG and examine the current state of AYA oncology research, the NCI, with support from the LIVESTRONG Foundation, sponsored a workshop entitled "Next Steps in Adolescent and Young Adult Oncology" on September 16 and 17, 2013, in Bethesda, Maryland. This report summarizes the findings from the workshop, opportunities to leverage existing data, and suggestions for future research priorities. Multidisciplinary teams that include basic scientists, epidemiologists, trialists, biostatisticians, clinicians, behavioral scientists, and health services researchers will be essential for future advances for AYAs with cancer.

Utilization of the Adolescent and Young Adult Psycho-Oncology Screening Tool in a Pediatric Hospital Adolescent/Young Adult Program.

Purpose: The AYA Psycho-Oncology Screening Tool was developed to assess adolescent and young adult (AYA) patients' distress during cancer treatment. The on-treatment distress screening tool has been validated with AYAs and includes a 10-point distress thermometer (DT) and a 53-item problem checklist (PCL). However, previous studies have not solely examined AYA cancer distress within a children's hospital. Therefore, our project aimed to explore AYA distress in a pediatric cancer setting. Methods: AYA-aged participants (aged ≥15) were given the distress screener initially within 1 month of diagnosis and every 2, 4, or 6 months, depending on their previous distress score. Chi-square, independent t-tests, and binary logistic regressions were conducted for data analysis. Results: Between January 2021 and July 2022, we completed 123 screenings in 68 AYAs (age 15-30) on treatment. Average DT score was 2.96 with 30% of participants endorsing distress levels of 5 and above. There were statistically significant differences by sex as females endorsed higher levels of distress compared with males. Adolescents (<18) endorsed statistically significant higher frequency of emotional PCL items in comparison with young adults (≥18). There were no differences by race or diagnosis. Conclusions: Our team gained awareness of specific areas of concerns for AYAs, allowing for more targeted interventions for distressed participants. Certain demographic variables may put participants at risk for increased distress. As a result of the project, a protocol has been developed to follow up with participants if they report a certain distress score (5 or above) and/or endorse critical items.

Expansion of the Fertility Preservation Program to All Newly Diagnosed Prepubertal Patients with Cancer at a Pediatric Hospital.

Background: As the majority of pediatric patients with cancer survive their disease, generating a population of over 500,000 childhood cancer survivors in the United States, it is imperative to minimize the lifelong consequences of treatment, which include temporary or permanent infertility caused by certain cancer treatments. A fertility consultation at diagnosis can provide patients and families with the opportunity to be informed regarding the likelihood of gonadal dysfunction and to consider fertility preservation. Method: After our pediatric hospital started to offer tissue cryopreservation, we initiated this evidence-based interventional quality improvement project. Our primary aim was to ensure that all newly diagnosed prepubertal patients with cancer who met the criteria for fertility tissue preservation were correctly identified and offered an educational consultation and preservation. Results: Between July 15, 2022 and October 30, 2022, 54 patients' treatment plans were evaluated to determine treatment-related infertility risk using the Oncofertility Consortium Pediatric Initiative Network's Risk Assessment tool. Fifteen patients were at a high level of significantly increased risk and 13 were eligible for consultation. Seven (46%) patients and their families received a consultation. Initiation of treatment before referral was the primary reason for lack of consultation. Six of seven patients receiving consultation (86%) elected to undergo preservation. Preservation procedures did not cause a delay in starting treatment for those patients. Discussion: A fertility preservation program with established policies and processes can increase the likelihood that prepubertal patients at high risk for infertility are correctly identified, educated, and offered preservation.

A Comprehensive Clinicopathologic and Molecular Reappraisal of GLI1-altered Mesenchymal Tumors with Pooled Outcome Analysis Showing Poor Survival in GLI1- amplified Versus GLI1-rearranged Tumors.

GLI1-altered mesenchymal tumor is a recently described distinct pathologic entity with an established risk of malignancy, being defined molecularly by either GLI1 gene fusions or amplifications. The clinicopathologic overlap of tumors driven by the 2 seemingly distinct mechanisms of GLI1 activation is still emerging. Herein, we report the largest series of molecularly confirmed GLI1-altered mesenchymal neoplasms to date, including 23 GLI1-amplified and 15 GLI1-rearranged new cases, and perform a comparative clinicopathologic, genomic, and survival investigation. GLI1-rearranged tumors occurred in younger patients (42 vs. 52 y) and were larger compared with GLI1-amplified tumors (5.6 cm vs. 1.5 cm, respectively). Histologic features were overall similar between the 2 groups, showing a multinodular pattern and a nested architecture of epithelioid, and less commonly spindle cells, surrounded by a rich capillary network. A distinct whorling pattern was noted among 3 GLI1-amplified tumors. Scattered pleomorphic giant cells were rarely seen in both groups. The immunoprofile showed consistent expression of CD56, with variable S100, CD10 and SMA expression. Genomically, both groups had overall low mutation burdens, with rare TP53 mutations seen only in GLI1-amplified tumors. GLI1-amplified mesenchymal tumors exhibit mostly a single amplicon at the 12q13-15 locus, compared with dedifferentiated liposarcoma, which showed a 2-peak amplification centered around CDK4 (12q14.1) and MDM2 (12q15). GLI1-amplified tumors had a significantly higher GLI1 mRNA expression compared with GLI1-rearranged tumors. Survival pooled analysis of current and published cases (n=83) showed a worse overall survival in GLI1-amplified patients, with 16% succumbing to disease compared with 1.7% in the GLI1-rearranged group. Despite comparable progression rates, GLI1-amplified tumors had a shorter median progression-free survival compared with GLI1-rearranged tumors (25 mo vs. 77 mo). Univariate analysis showed that traditional histologic predictors of malignancy (mitotic count ≥4/10 high-power fields, presence of necrosis, and tumor size ≥5 cm) are associated with worse prognosis among GLI1-altered mesenchymal tumors.

Neighborhood-level social determinants of health burden among adolescent and young adult cancer patients and impact on overall survival.

BACKGROUND: Neighborhood socioeconomic deprivation has been linked to adverse health outcomes, yet it is unclear whether neighborhood-level social determinants of health (SDOH) measures affect overall survival in adolescent and young adult patients with cancer. METHODS: This study used a diverse cohort of adolescent and young adult patients with cancer (N = 10 261) seen at MD Anderson Cancer Center. Zip codes were linked to Area Deprivation Index (ADI) values, a validated neighborhood-level SDOH measure, with higher ADI values representing worse SDOH. RESULTS: ADI was statistically significantly worse (P < .050) for Black (61.7) and Hispanic (65.3) patients than for White patients (51.2). Analysis of ADI by cancer type showed statistically significant differences, mainly driven by worse ADI in patients with cervical cancer (62.3) than with other cancers. In multivariable models including sex, age at diagnosis, cancer diagnosis, and race and ethnicity, risk of shorter survival for people residing in neighborhoods with the least favorable ADI quartile was greater than for individuals in the most favorable ADI quartile (hazard ratio = 1.09, 95% confidence interval = 1.00 to 1.19, P = .043). CONCLUSION: Adolescent and young adult patients with cancer and the worst ADI values experienced a nearly 10% increase in risk of dying than patients with more favorable ADI values. This effect was strongest among White adolescent and young adult survivors. Although the magnitude of the effect of ADI on survival was moderate, the presence of a relationship between neighborhood-level SDOH and survival among patients who received care at a tertiary cancer center suggests that ADI is a meaningful predictor of survival. These findings provide intriguing evidence for potential interventions aimed at supporting adolescent and young adult patients with cancer from disadvantaged neighborhoods.

Randomized Clinical Trial of a Self-care and Communication Intervention for Parents of Adolescent/Young Adults Undergoing High-Risk Cancer Treatment: A Report From the Children's Oncology Group.

BACKGROUND: Parents of adolescents and young adults (AYAs) with cancer offer primary support to their children and often experience their own high levels of distress, affecting parent-AYA communication and quality of life. OBJECTIVE: To reduce parent distress and improve communication during high-risk cancer treatment, we examined efficacy of a self-care and communication intervention for parents and indirect benefit for AYAs receiving a therapeutic music video (TMV) intervention. METHODS: In this study, we conducted a multisite, randomized controlled trial with AYAs and parents enrolled as dyads (n = 110). Parents were randomized to intervention or low-dose control; all AYAs received TMV. Data collection occurred at baseline, 2 weeks post intervention (T2), and 90 days post intervention (T3). RESULTS: There were no significant between-group differences on primary outcomes for parents or AYAs. We did find significant differences favoring the parent intervention group on parenting confidence at T2 and marginally better outcomes for family adaptability/cohesion at T3. Both groups exhibited significant within-group improvement for parent distress (state anxiety, T3; perceived stress, T2 and T3; mood, T3), state anxiety (T2) intervention only, and family strengths control group only. Qualitative data demonstrate the parent intervention raised self-awareness and parent confidence in the short term. CONCLUSION: Parents found their intervention helpful. Absence of significant results may be due to short intervention duration, need for tailored content, underpowered sample, and potential indirect parent benefit from AYA participation in TMV. The parent intervention did not provide an indirect benefit for AYAs. IMPLICATIONS FOR NURSING: Parents identified their own need for communication and support from nurses. Nurses can optimize AYA care by attending to parent needs through supportive listening and encouraging self-care.

Fatigue, sleep-wake disturbances, and quality of life in adolescents receiving chemotherapy.

BACKGROUND: Adolescents with cancer experience distressing physical and psychosocial symptoms, especially during treatment. Fatigue and sleep disturbances commonly affect adolescents' quality of life, but little is known about how adolescents experience these symptoms during an early month of chemotherapy. This study measured fatigue, sleep disturbances, and quality of life in 20 adolescents over 1 month while they were receiving chemotherapy. METHODS: Multidimensional fatigue and quality of life were measured weekly with modules from the PedsQL Measurement Model, and sleep disturbances were measured with the General Sleep Disturbance Scale. RESULTS: Adolescents experienced increased severity of fatigue and sleep disturbances during the week after treatment. Common sleep-wake problems included daytime sleepiness, decreased alertness, and poor sleep quality. Fatigue and sleep-wake disturbances were related symptoms, and both symptoms were associated with various domains of quality of life. CONCLUSIONS: Fatigue and sleep-wake disturbances are significant problems for adolescents receiving chemotherapy and negatively affect the quality of life. Clinicians should routinely screen adolescent patients for fatigue and sleep disturbances and intervene to minimize their impact using pharmacologic and nonpharmacologic strategies.

Disparities in Cancer Care: The Example of Sarcoma-In Search of Solutions for a Global Issue.

Disparities in health care have an adverse effect on the outcome of disadvantaged patients with cancer. Patients may be at a disadvantage because of geographic isolation; insurance status; or racial, ethnic, or other factors. In this article, we examine how disparities affect the care of patients with sarcoma in the United States, Canada, and the Asia-Pacific region. Because of the rarity of sarcomas and their challenging diagnosis and complex treatment patterns, some professional or national guidelines stipulate that patients with sarcoma should be treated at centers of expertise by multidisciplinary teams. This recommendation, based on published evidence, is not always applicable because of various sociopolitical or patient-related factors. We are proposing solutions to overcome these obstacles in a practical and patient-centered way while acknowledging that disparities exist among countries as well as within any country.

The adolescence of young adult oncology.

The clinical care of young adults with cancer, and related research, was a novel focus of oncology a decade ago, but 10 years of data on patients' needs and outcome disparities, well-reviewed in the articles of this special issue and its predecessor (June 2009), prove the merit of this subspecialty. The field, emerging from its childhood and entering adolescence, must continue to look to the future to solidify its worth. In this concluding article we examine important themes that must receive attention for the discipline to develop and flourish. We must overcome the challenges inherent in serving a population that is difficult to define, and which crosses traditional boundaries and disciplines. The field must strengthen its research in clinical trials and comparative outcomes, and must articulate the key competencies that distinguish a practitioner of young adult oncology (both to define clinical programs and educational curricula). Key opportunities are collaborations with leaders in oncofertility, developmental psychology, and transitional care, and with patient advocates. We must garner support from federal entities, as well as philanthropic agencies and accrediting bodies. With strategic effort, the field of young adult oncology will mature and grow wise.

Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib.

BACKGROUND: Sunitinib inhibits KIT and other members of the split-kinase-domain family of receptor tyrosine kinases. Sunitinib prolongs survival in adult patients with imatinib-resistant gastrointestinal stromal tumor (GIST). We report the experience with sunitinib in pediatric patients with advanced GIST following failure of imatinib. PROCEDURE: Sunitinib therapy was provided through a treatment-use protocol. Patients were 10-17 years old at enrollment. All patients had GIST resistant to imatinib therapy. Sunitinib was administered daily for 4 weeks in 6-week treatment cycles. KIT and platelet-derived growth factor receptor alpha (PDGFRA) genotyping of tumor tissue were performed. RESULTS: One patient achieved a partial response, five patients had stable disease and one patient had progressive disease on sunitinib. The duration of disease stabilization was between 7 and 21+ months, with a mean of 15 months. Time to tumor progression was longer on sunitinib than on prior imatinib treatment for five of six patients. Two patients experienced grade 3 adverse events. All other adverse events were grade 1-2. None of the five patients tested had mutations in KIT or PDGFRA. CONCLUSION: Sunitinib treatment was associated with substantial initial antitumor activity and acceptable tolerability in this group of pediatric patients with imatinib-resistant GIST.

Access to care.

Rapid diagnosis, timely initiation of optimal treatment and good supportive care should be the gold standard for all patients who develop cancer, irrespective of age and where they live. This article reviews the evidence that teenagers/adolescents and young adults may be disadvantaged with regard to access to care. Delays in diagnosis and the reasons for them (patient and professional), low enrolment into clinical trials, suboptimal treatment strategies and place of care are addressed. We must access the voice of the young, address their needs, and involve them more in decisions concerning their own health. Progress is being made slowly in several countries and international collaboration linking patients, health care professionals, governmental and non-governmental agencies is essential. Such international collaboration and focus, with specific research goals are suggested in order to make variation in access to optimal care become a thing of the past.

Reducing irinotecan-associated diarrhea in children.

Irinotecan is increasingly being used in pediatric oncology. Amelioration of diarrhea associated with protracted irinotecan administration may reduce morbidity and improve dose intensity. In this review, we discuss what is known about the pathogenesis of this toxicity as well as potential predisposing genetic factors. We comprehensively summarize the literature regarding available prevention and treatment strategies, and report data on the use of cephalosporin prophylaxis in 51 patients treated on various pediatric trials. This approach is feasible in children and allows for tolerance of higher doses of protracted irinotecan.

Recall of Fertility Discussion by Adolescent Female Cancer Patients: A Survey-Based Pilot Study.

Many adolescent female cancer patients will survive into their reproductive years. Pediatric oncologists are advised to discuss oncofertility during treatment planning. In this pilot study, 19 adolescent females completed a retrospective survey assessing recall of a fertility discussion, satisfaction with fertility knowledge, and multiple factors that may influence recall, including parental involvement in decision-making. Eleven respondents (58%) remembered a discussion about infertility risk and 9 (47%) about fertility preservation. Most who recalled a discussion were satisfied with their fertility knowledge (10/11, 90.9%). In this study, we validated the feasibility of survey administration and identified trends in oncofertility counseling at our center.

Primary Care Physicians' Decision Making Regarding Initial Oncology Referral for Adolescents and Young Adults With Cancer.

PURPOSE: The objectives of this study were to determine whether pediatricians are more likely than other primary care physicians (PCPs) to refer newly diagnosed adolescent and young adult patients with cancer to pediatric oncological specialists, and to assess the physician and patient characteristics that affect patterns of referral. METHODS: A cross-sectional vignette survey was mailed to PCPs to examine hypothetical referral decisions as a function of physician characteristics and patient characteristics, including diagnosis, age, gender, race/ethnicity, family support, transportation, insurance, and patient preference for site of care. Pediatrician PCPs and nonpediatrician PCPs (family medicine, internal medicine, and emergency medicine physicians) practicing in North Carolina and in Washington State participated in the study. RESULTS: A total of 406 surveys were completed (35.8% response rate). Sixty percent of pediatric PCPs referred their hypothetical patients with cancer to pediatric specialists (PSs), compared with only 37% of nonpediatric PCPs. Patient age also influenced referral patterns; 89% of 13-year-olds, 74% of 16-year-olds, 25% of 19-year-olds, and only 9% of 22-year-old patients were referred to a PS. Multivariate logistic regression demonstrated that diagnosis and physician practice setting also were associated with referral patterns. CONCLUSIONS: Both patient age and PCP specialty were significant predictors of referral patterns in hypothetical vignettes of newly diagnosed adolescent and young adult patients with cancer. Pediatricians were more likely than nonpediatrician PCPs to refer patients to a PS. Referrals to PSs decreased dramatically between ages 16 and 19. Because the site of oncological care can impact outcomes, these data have the potential to inform awareness and education initiatives directed at PCPs.

Prevalence and Predictors of Sperm Banking in Adolescents Newly Diagnosed With Cancer: Examination of Adolescent, Parent, and Provider Factors Influencing Fertility Preservation Outcomes.

Purpose To estimate the prevalence of sperm banking among adolescent males newly diagnosed with cancer and to identify factors associated with banking outcomes. Patients and Methods A prospective, single-group, observational study design was used to test the contribution of sociodemographic, medical, psychological/health belief, communication, and developmental factors to fertility preservation outcomes. At-risk adolescent males (N = 146; age 13.00 to 21.99 years; Tanner stage ≥ 3), their parents, and medical providers from eight leading pediatric oncology centers across the United States and Canada completed self-report questionnaires within 1 week of treatment initiation. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs for specified banking outcomes (collection attempt v no attempt and successful completion of banking v no banking). Results Among adolescents (mean age, 16.49 years; standard deviation, 2.02 years), 53.4% (78 of 146) made a collection attempt, with 43.8% (64 of 146) successfully banking sperm (82.1% of attempters). The overall attempt model revealed adolescent consultation with a fertility specialist (OR, 29.96; 95% CI, 2.48 to 361.41; P = .007), parent recommendation to bank (OR, 12.30; 95% CI, 2.01 to 75.94; P = .007), and higher Tanner stage (OR, 5.42; 95% CI, 1.75 to 16.78; P = .003) were associated with an increased likelihood of a collection attempt. Adolescent history of masturbation (OR, 5.99; 95% CI, 1.25 to 28.50; P = .025), banking self-efficacy (OR, 1.23; 95% CI, 1.05 to 1.45; P = .012), and parent (OR, 4.62; 95% CI, 1.46 to 14.73; P = .010) or medical team (OR, 4.26; 95% CI, 1.45 to 12.43; P = .008) recommendation to bank were associated with increased likelihood of sperm banking completion. Conclusion Although findings suggest that banking is underutilized, modifiable adolescent, parent, and provider factors associated with banking outcomes were identified and should be targeted in future intervention efforts.

Phase II study of doxorubicin and bevacizumab for patients with metastatic soft-tissue sarcomas.

PURPOSE: To evaluate the antitumor activity and tolerability of bevacizumab and doxorubicin in patients with metastatic soft-tissue sarcoma (STS). PATIENTS AND METHODS: Patients may have had up to one nonanthracycline line of therapy. Seventeen patients with metastatic STS were treated with doxorubicin at 75 mg/m2 intravenous (IV) push followed by bevacizumab 15 mg/kg IV every 3 weeks. Dexrazoxane was started for total doxorubicin dose exceeding 300 mg/m2. RESULTS: A total of 85 cycles of doxorubicin/bevacizumab were administered, median four cycles (range, one to 11), with three patients receiving one to four cycles of bevacizumab maintenance after reaching 600 mg/m2 doxorubicin. All 17 patients were assessable for response. Two partial responses (12%, 95% CI = 1% to 36%) were observed, lasting seven and 12 cycles of therapy. Eleven patients (65%) had stable disease for four cycles or more. Six patients developed cardiac toxicity grade 2 or greater, with four patients grade 2 (cumulative doxorubicin 75, 150, 300, 300 mg/m2, respectively), one grade 3 (total doxorubicin 591 mg/m2), and one grade 4 (total doxorubicin 420 mg/m2). One patient with extensive lung disease died of recurrent bilateral pneumothoraces, possibly treatment-related. CONCLUSION: The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease lasting four cycles or longer suggests further study is warranted in STSs. The observed cardiac toxicity, despite close monitoring and standard use of dexrazoxane, obliges a change in the dose and/or schedule in future studies of this combination.