Time to diagnosis among young patients with cancer.

BACKGROUND: Sociodemographic and clinical factors associated with diagnostic delays in pediatric, adolescent, and young adult cancers are poorly understood. METHODS: Using the Optum Labs Data Warehouse's de-identified claims data for commercial health plan enrollees, we identified children (0-14 years) and adolescents/young adults (AYAs) (15-39 years) diagnosed with one of 10 common cancers from 2001 to 2017, who were continuously enrolled for 6 months preceding diagnosis. Time to diagnosis was calculated as days between first medical encounter with possible cancer symptoms and cancer diagnosis date. Median times from first symptom to diagnosis were compared using Wilcoxon rank sum test. Multivariable unconditional logistic regression identified sociodemographic factors associated with longer time (>3 months) to cancer diagnosis (from symptom onset). RESULTS: Of 47,296 patients, 87% presented prior to diagnosis with symptoms. Patients with central nervous system (CNS) tumors were most likely to present with symptoms (93%), whereas patients with cervical cancer were least likely (70%). Symptoms varied by malignancy. Of patients with symptoms, thyroid (105 days [range: 50-154]) and cervical (104 days [range: 41-151]) cancer had the longest median time to diagnosis. Females and patients at either end of the age spectrum were more likely to experience diagnosis delays of more than 3 months. CONCLUSION: In a commercially insured population, time to diagnosis varies by cancer type, age, and sex. Further work is needed to understand the patient, provider, and health system-level factors contributing to time from symptom onset to diagnosis, specifically in the very young children and the young adult patient population going forward.

The Effect of COVID-19 on Oncology Care for Adolescents and Young Adults in Latin America.

Children with cancer in low- and middle-income countries were disproportionately impacted by the COVID-19 pandemic, but little is known about how adolescents and young adults (AYAs) with cancer were affected. Sixty-seven physicians and nonphysician providers were interviewed about their experiences caring for AYAs with cancer in Latin America. Quotes related to the COVID-19 pandemic were identified and grouped into themes. Barriers from the COVID-19 pandemic included limited space, restrictions on travel, reduced funding, limited staff, limited services, and changes to treatment. However, improvements to care that arose from the COVID-19 pandemic included better access to distance learning and telemedicine.

Effect of ALDH1A1 and CD44 on Survival and Disease Recurrence in Patients With Osteosarcoma.

PURPOSE: Emerging evidence suggests that osteosarcoma stem cells (OSCs) may be responsible for tumor initiation propagation, recurrence, and resistance to therapy. We set out to evaluate the relationship between the abundance of ALDH1A1 and CD44-positive cells in biopsy and resection samples on disease recurrence and overall survival. METHODS: A retrospective review of 20 patients, including biopsy and resection samples, was performed at a comprehensive cancer center. Additionally, we queried the publicly available TARGET dataset of osteosarcoma patients. RESULTS: Neither the percentages of ALDH1A1-positive cells nor CD44-positive cells were significantly associated with overall mortality or disease recurrence in either biopsy or resection samples. Unlike our institutional data, overall survival was significantly correlated to higher ALDH1A1 expression in the TARGET dataset both in univariate and age-adjusted analyses. CONCLUSIONS: ADLH1 and CD44, potential markers of OSCs, were not found to be reliable clinical immunohistochemical prognostic markers for osteosarcoma patient survival, specifically disease-free survival. Osteosarcoma patients with high ALDH1A1 RNA expression showed improved overall survival in examining a national genomic database of osteosarcoma patients but again no association with disease-free survival. The potential of CD44 and ALDH1A1 as cellular-specific prognostic markers of survival, and as possible molecular targets, may be limited in osteosarcoma.

Receipt of Guideline-Concordant Care Is Associated With Improved Survival in Patients With Osteosarcoma in California: A Population-Based Analysis.

PURPOSE: To examine the relationship between guideline-concordant care (GCC) on the basis of national clinical practice guidelines and survival in children (0-14 years), adolescents and young adults (AYAs, 15-39 years), and adults (40 years and older) with osteosarcoma, and to identify sociodemographic and clinical factors associated with receipt of GCC and survival. METHODS: We used data from the California Cancer Registry (CCR) on patients diagnosed with osteosarcoma during 2004-2019, with detailed treatment information extracted from the CCR text fields, including chemotherapy regimens. Multivariable logistic and Cox proportional hazard regression were used for statistical analyses. RESULTS: Of 1,716 patients, only 47% received GCC, with variation by age at diagnosis: 67% of children, 43% of AYAs, and 30% of adults. In multivariable models, patients who received part or all care (v none) at specialized cancer centers were more likely to receive GCC. AYAs and adults were less likely to receive GCC than children (odds ratio [OR], 0.38 [95% CI, 0.30 to 0.50] and OR, 0.40 [95% CI, 0.28 to 0.56], respectively). In a model excluding adults, patients treated by pediatric (v medical) oncologists were more likely to receive GCC (OR, 3.44 [95% CI, 2.40 to 4.94]). Patients with metastatic osteosarcoma at diagnosis who did not receive GCC had a greater hazard of death (hazard ratio [HR], 2.02 [95% CI, 1.55 to 2.63]) but no statistical differences were found in those diagnosed at earlier stages (HR, 1.15 [95% CI, 0.92 to 1.43]). CONCLUSION: GCC was associated with improved survival in patients with metastatic osteosarcoma in California. However, we found disparities in the delivery of GCC, highlighting the need for target interventions to improve delivery of GCC in this patient population.

Survival Trends Among Adolescents and Young Adults Diagnosed With Cancer in the United States: Comparisons With Children and Older Adults.

PURPOSE: Although data from 1975 to 1997 revealed a gap in cancer survival improvement in adolescents and young adults (AYAs; 15-39 years) compared with children and older adults, more recent studies have reported improvements in AYA cancer survival overall. The current analysis provides an update of 5-year relative survival and cancer survival trends among AYAs compared with children and older adults. METHODS: We obtained data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program for 17 regions to obtain recent (2010-2018) 5-year relative survival estimates by cancer type, stage, sex, and race/ethnicity by age group. In addition, we calculated 5-year relative survival trends during 2000-2014. RESULTS: Across 33 common AYA cancers, AYAs and children had high 5-year relative survival (86%) and experienced similar survival improvements over time (average absolute change: AYAs, 0.33%; children 0.36%). Among AYAs, 73% of cancers had improvement in 5-year relative survival since 2000. Despite this overall progress, we identified cancers where survival was worse in AYAs than younger or older patients and cancers that have had either a lack of improvement (osteosarcoma and male breast) or decreases in survival (cervical and female bladder) over time. Furthermore, males had inferior survival to females for all cancers, except Kaposi sarcoma and bladder cancer, and non-Hispanic Black/African American AYAs experienced worse survival than other racial/ethnic groups for many cancers considered in this study. CONCLUSION: Future studies should focus on identifying factors affecting survival disparities by age, sex, and race/ethnicity. Differences in biology, clinical trial enrollment, delivery of treatment according to clinical guidelines, and supportive and long-term survivorship care may account for the survival disparities we observed and warrant further investigation.

How Do Adolescent and Young Adult Patients with Cancer Manage Their Chemotherapy-Related Symptoms at Home?

Chemotherapy can cause many distressing side effects, potentially impacting treatment completion and quality of life in adolescent and young adult (AYA) patients with cancer. To identify ways to help mitigate chemotherapy-related symptoms, we sought to elicit barriers and facilitators to managing symptoms experienced by AYAs with cancer through interviews. Qualitative thematic analysis identified three main domains: (1) managing chemotherapy symptoms (e.g., medication, home remedies), (2) anticipating and mitigating symptoms (e.g., management of symptoms at home, anticipatory guidance), and (3) knowing when to seek care (e.g., unexpected and unusual symptoms). This study elucidated that AYAs can successfully manage symptoms at home when given the proper guidance and this could be a focus of future efforts to improve outcomes in this population. The Clinical Trial Registration number is NCT04594096.

Update on the Role of Imaging in Staging of Common Pediatric Abdominal Tumors.

Neuroblastoma, Wilms tumor, and hepatoblastoma are the most common pediatric abdominal malignancies. Management of these diseases is a multidisciplinary process that continues to evolve based on the results of international collaborative trials and advances in understanding of tumor biology. Each of these tumors has unique characteristics and behavior which are reflected in their respective staging systems. It is important for clinicians involved in the care of children with abdominal malignancies to be familiar with current staging guidelines and imaging recommendations. This article reviews the current role of imaging in the management of these common pediatric abdominal malignancies, with emphasis on initial staging.

Localized Synovial Sarcoma: A Population-Based Analysis of Treatment Patterns and Survival.

Purpose: Synovial sarcoma (SS) is a rare, high-grade soft tissue tumor that requires multidisciplinary and multimodal care with surgery, radiotherapy, and chemotherapy. We examined the impact of sociodemographic and clinical factors on treatment patterns and survival in localized SS patients. Methods: Adolescents and young adults (AYAs, 15-39 years) and older adults ("adults," ≥40 years) diagnosed with localized SS from 2000 to 2018 were identified in the California Cancer Registry. Multivariable logistic regression identified clinical and sociodemographic factors associated with receipt of chemotherapy and/or radiotherapy. Cox proportional hazards regression identified factors associated with overall survival (OS). Results are reported as odds ratios (ORs) and hazard ratios (HRs), respectively, with 95% confidence intervals (CIs). Results: More AYAs (n = 346) than adults (n = 272) received chemotherapy (47.7% vs. 36.4%) and radiotherapy (62.1% vs. 58.1%). Age at diagnosis, tumor size, treatment at National Cancer Institute-Children's Oncology Group (NCI-COG)-designated facilities, insurance status, and neighborhood socioeconomic status (SES) influenced treatment patterns. Among AYAs, treatment at NCI-COG-designated facilities was associated with receiving chemotherapy (OR 2.74, CI 1.48-5.07) and low SES was associated with worse OS (HR 2.28, 1.09-4.77). In adults, high SES was associated with receiving chemoradiotherapy (OR 3.20, CI 1.40-7.31), whereas public insurance was associated with decreased odds of chemoradiotherapy (OR 0.44, CI 0.20-0.95). With regard to treatment, absence of radiotherapy (HR 1.94, CI 1.18-3.20) was associated with worse OS in adults. Conclusion: In localized SS, both clinical and sociodemographic factors influenced treatment patterns. Further research should investigate how SES-related factors produce treatment disparities and identify interventions to improve treatment equity and outcomes.

Lymph node metastases in paediatric and young adult patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS): Findings from Children's Oncology Group (COG) study ARST0332.

PURPOSE: The aim of this paper is to better define the clinical features and outcomes of young patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) with regional and distant lymph node (LN) metastases treated in a standardised fashion, we analysed LN involvement in COG study ARST0332, which evaluated a risk-based treatment strategy for young patients with all stages of NRSTS. PATIENTS AND METHODS: Patients <30 years old with newly diagnosed NRSTS and LN metastases enrolled on ARST0332 were studied. Regional LN sampling was required for those with epithelioid sarcoma, clear cell sarcoma or clinically/radiographically enlarged LNs. Tumour features and extent of pre-enrolment resection determined treatment, including chemotherapy, radiotherapy, and delayed surgery. Recommendations for LN metastases included LN dissection at the time of primary tumour resection and dose-adapted radiotherapy based on extent of LN resection. RESULTS: Twenty of 529 eligible and evaluable ARST0332 patients with NRSTS had LN metastases; epithelioid sarcoma had the highest incidence (18%, 5 of 28). Pre-treatment imaging identified LN enlargement in 19 of 20 patients; 1 had no pre-treatment LN imaging. At 6.9 years median follow-up for surviving patients, 5-year overall survival was 85.7% (95% CI: 33.4%, 97.9%) for seven patients with isolated LN metastases and 15.4% (95% CI: 2.5%, 38.8%) for 13 patients with additional extranodal metastases. LN recurrence occurred in only one patient without LNs sampled at initial diagnosis. CONCLUSION: LN metastases occur in about 4% of paediatric/young adult NRSTS, are limited to a few histologic subtypes, and are rare in patients who did not have clinical or imaging evidence of lymphadenopathy, suggesting that biopsies of non-enlarged LNs are not necessary to identify occult involvement. Patients with isolated LN metastases have high 5-year overall survival (∼85%) and should be treated with curative intent. GOV REGISTRY NO: NCT00346164.

Treatment-related toxicities associated with hospitalization in children, adolescents, and young adults with acute lymphoblastic leukemia: population level analysis.

Treatment-related toxicities (TRTs) are a potential cause of survival disparities in patients with acute lymphoblastic leukemia (ALL). We aimed to identify the most frequent TRTs associated with hospitalizations at a population level in children, adolescents and young adults (AYAs). We used the California Cancer Registry linked to a statewide hospital discharge database to identify children and AYAs with TRTs within 3 years of diagnosis. We assessed the frequency of TRTs, length of stay (LOS), admission rates associated with TRTs and TRTs impact on survival. Febrile neutropenia, hypertension, and thrombocytopenia were the most common TRTs for both children and AYAs. AYAs had longer median LOS compared to children for most toxicities. AYAs at non-specialized cancer centers (SCCs) had higher frequency of admissions associated with TRTs compared to non-SCC. Cardiovascular, respiratory, gastrointestinal, renal, and infectious TRTs were associated with worse survival. This study demonstrates the burden of TRTs in patients with ALL.

Impact of local treatment modality on overall- and disease-specific survival for nonmetastatic pelvic and sacral Ewing sarcoma.

PURPOSE: The ideal local treatment modality for pelvic and sacral Ewing sarcoma (EWS) is controversial. METHODS: We present the data from the American College of Surgeon's National Cancer Database (NCDB) and the National Cancer Institute's Surveillance, Epidemiology and End Result (SEER) database to investigate the impact of local treatment modalities on survival for nonmetastatic pelvic and sacral Ewing sarcoma. Local treatment includes "surgery," "radiation," and a combination of "surgery and radiation." RESULTS: A total of 235 cases from SEER and 285 cases from NCDB were analyzed. Patients with "localized" stage (intraosseous) in the SEER database did not show any statistically significant difference in the disease-specific survival (DSS) for any of the local treatment modalities. Similar findings were observed for overall survival among patients with American Joint Committee on Cancer (AJCC) stage II and III in the NCDB database. However, patients with nonmetastatic disease, particularly regional disease (extraosseous), showed improved DSS with surgery only, in the SEER. CONCLUSION: We found similar levels of efficacy for different treatment modalities for patients with intraosseous and AJCC II and III pelvic and sacral EWS. "Radiotherapy" is the most common local treatment modality employed in the United States. A prospective, randomized controlled trial with a direct head-to-head comparison is needed for a definitive conclusion.

Non-Private Health Insurance Predicts Advanced Stage at Presentation and Amputation in Lower Extremity High Grade Bone Sarcoma: A National Cancer Database Study : Amputation Predicts Survival: An Effect Most Pronounced in Pediatric and AYA Age Group.

INTRODUCTION: Advances in diagnostic and treatment modalities for high grade bone sarcomas (HGBS) of lower extremity (LE) have enabled limb salvage resections as a feasible first-line surgical option. However, amputations are still performed. Impact of amputation on survival and predictive factors for amputation and the stage at presentation for HGBS of LE remain unknown. METHODS: National Cancer Database was used to extract 5781 cases of high-grade bone sarcoma of the LE from 2004 to 2017. Kaplan-Meier and Cox regression were used to determine the impact of amputation on survival. Chi square test and logistic regression were used to assess the correlation of predictive factors with amputation and stage at presentation. RESULTS: Amputation [hazard ratio (HR) 1.516; 95% confidence interval (CI) 1.259-1.826; p < 0.001] and advanced stage (HR 0.248; 95% CI 0.176-0.351; p < 0.001) were independent predictors of poor overall survival. The impact of amputation on survival was most pronounced for pediatric and adolescents and young adults (AYA) age groups (18% decrease in 10-year survival). Amputation was more likely to be performed among those with nonprivate insurance (HR 1.736; 95% CI 1.191-2.531; p = 0.004), a finding that was mirrored for advanced stage at presentation (HR 0.611; 95% CI 0.414-0.902; p = 0.013). DISCUSSION: Amputation is an independent predictor of poor outcomes among patients with HGBS of LE. The impact of amputation on survival is the highest for the pediatric and AYA age group. Nonprivate insurance is associated with increased likelihood of amputation and an advanced stage at presentation among patients with high-grade bone sarcoma of the LE. This is the largest study highlighting insurance-related disparities in this cohort.

A qualitative study of barriers and facilitators to adolescents and young adults' participation in cancer clinical trials: Oncologist and patient perspectives.

BACKGROUND: Despite efforts to increase participation of adolescents and young adults (AYAs; 15-39 years) in cancer clinical trials (CTs), enrollment remains very low. Even when provided access to CTs, AYAs are less likely to participate than children and older adults. A better understanding of oncologist- and AYA survivor-reported barriers, facilitators, and potential areas for CT enrollment improvement is needed. PROCEDURES: From December 2019 to August 2020, we conducted 43 semi-structured interviews with oncologists (n = 17) and AYA cancer survivors (n = 26) who were offered and/or participated in CTs at cancer centers in California and Utah. Thematic analyses were used to interpret the findings. RESULTS: Oncologists identified a lack of available CTs, strict eligibility criteria, lack of awareness of open CTs, and poor communication between pediatric and adult oncologists as major barriers to enrollment. AYA cancer survivors identified financial and psychosocial barriers, and a poor understanding of what a CT means and its potential benefits as barriers to enrollment. Areas for improvement identified by oncologists and AYAs include educational, financial, and psychosocial support to AYAs. Oncologists also emphasized the need to increase CT availability, improve awareness of open CTs, and better communication between both pediatric and adult oncologists and oncologists and AYAs. CONCLUSIONS: For AYAs with cancer, a lack of CT eligibility and physician awareness of open CTs likely factor into their lower CT enrollment. Potential strategies to improve AYA enrollment in CTs require comprehensive collaboration between pediatric and adult institutions, as well as educational, psychosocial, and financial support to AYAs.

Treatment at Specialized Cancer Centers Is Associated with Improved Survival in Adolescent and Young Adults with Soft Tissue Sarcoma.

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors whose management benefits from a multidisciplinary therapeutic approach. Published data suggest that cancer treatment at a specialized cancer center (SCC) can improve survival in other cancers. Therefore, we examined the impact of the location of treatment on survival in children and adolescents and young adults (AYAs) with STS. Methods: We performed a population-based analysis of children and AYAs hospitalized within 1 year of diagnosis with first primary STS (2000-2014) using the California Cancer Registry linked with hospitalization data. Patients were categorized based on receiving all inpatient treatments at a SCC versus part/none. Multivariable Cox proportional hazards regression identified factors associated with overall and STS-specific survival by age group. Results are presented as adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Of the 1,674 patients with STS, 142 were children (0-14) and 1,532 were AYAs (15-39) and 89.4% and 40.4% received all inpatient treatments at a SCC, respectively. Overall, the 5-year survival was improved for patients who received all inpatient care at a SCC (59.8% vs. those who received part/none, 50.7%). Multivariable regression analysis found that having all treatments at a SCC was associated with better overall survival (HR, 0.79, CI: 0.65-0.95) in AYAs, but not in children. Conclusions: Our findings demonstrate that treatment for STS at a SCC is associated with better survival in AYAs. Eliminating barriers to treatment of AYAs with STS at SCCs could improve survival in this population.

Initial cancer treatment and survival in children, adolescents, and young adults with Hodgkin lymphoma: A population-based study.

BACKGROUND: Hodgkin lymphoma (HL) is a treatable tumor affecting children, adolescents and young adults (AYAs; 15-39 years old). Population-based studies report worse survival for non-White children and AYAs but have limited data on individual therapeutic exposures. This study examined overall and HL-specific survival in a population-based cohort of patients while adjusting for sociodemographic factors and treatment. METHODS: Data for 4807 patients younger than 40 years with HL (2007-2017) were obtained from the California Cancer Registry. Individual treatment information was extracted from text fields; chemotherapy regimens were defined by standard approaches for pediatric and adult HL. Multivariable Cox models examined the influence of patient and treatment factors on survival. RESULTS: At a median follow-up of 4.4 years, 95% of the patients were alive. Chemotherapy differed by age, with 70% of 22- to 39-year-olds and 41% of <22-year-olds receiving doxorubicin, bleomycin, vinblastine, and dacarbazine (P < .001). In multivariable models, older patients (22-39 vs < 21 y; hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.11-2.10), Black (vs White patients); HR, 1.90; 95% CI, 1.25-2.88), and Hispanic patients (HR, 1.45; 95% CI, 1.06-1.99) experienced worse survival; among those < 21 y, Black race was associated with a 3.3-fold increased risk of death (HR, 3.26; 95% CI, 1.43-7.42). CONCLUSIONS: In children and AYAs with HL, older age and non-White race/ethnicity predicted worse survival after adjustments for treatment data. Further work is needed to identify the biological and nonbiological factors driving disparities in these at-risk populations.

Prognostic factors, disparity, and equity variables impacting prognosis in bone sarcomas of the hand: SEER database review.

BACKGROUND: Primary sarcomas originating from the bones of hand and wrist are rare but carry a significant burden of morbidity. METHODS: National Cancer Institute's Surveillance, Epidemiology and End Result database from 1975 to 2017 was queried to report incidence and survival data in 237 patients in the United States. Kaplan-Meier and Cox regression were used to determine the prognostic factors affecting survival. χ2 test was used to assess the correlation. RESULTS: Incidence of hand and wrist sarcoma was 0.017 per 100 000 persons in 2017 and has not significantly changed since 1975 (p > 0.05). Disease-specific 5-year and 10-year survival for the entire cohort was 90% and 84%, respectively. On multivariate analysis race "others," histology other than "osteosarcoma," "undifferentiated" grade, and size "≥6 cm" were predictors of worse disease-specific survival. Cross-tabulation of race with other significant prognostic factors on univariate analysis revealed a significant correlation of race with every other significant prognostic factor except for grade. CONCLUSIONS: The current study is an analysis of a population-based registry reporting incidence and survival data for patients with sarcoma of hand and wrist. Independent prognostic factors include race, histology, grade, and size. There is a lack of improvement in survival over the last four decades.