Adolescents and young adults with rhabdomyosarcoma: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

INTRODUCTION: The impact of established prognostic factors on survival outcomes for childhood rhabdomyosarcoma (RMS) have not been well described in the adolescent and young adult (AYA) RMS patient population. METHODS: This is a retrospective analysis of patients with newly diagnosed RMS enrolled between 1997 and 2016 on seven previously reported Children's Oncology Group (COG) clinical trials. Demographics, clinical features, treatment details, and outcome data were collected. Five-year event-free survival (EFS) and overall survival (OS) were estimated for patients diagnosed at age 15-39 years and those diagnosed under age 15 years using the Kaplan-Meier method. Log-rank test was used to compare prognostic factors for EFS and OS. Factors significant in the univariable analysis were included in a Cox proportional hazards regression model. Nonsignificant covariates were removed from the multiple regression model. RESULTS: Total 2151 patients including 402 AYAs were analyzed. AYAs were more likely to present with primary tumors ≥5 cm in size, metastatic disease, alveolar histology, and have FOXO1 fusions compared to children. Five-year EFS for the AYA cohort was 44.2% versus 67% for children (p < .001), and 5-year OS was 52% for the AYA cohort versus 78% for children (p < .001). Multivariable analysis revealed tumor site, size and invasiveness, clinical group, and histology were prognostic in AYAs. CONCLUSION: AYAs with RMS have a poorer prognosis compared to younger children due to multiple factors. Further research focused on AYAs to better understand RMS biology and improve treatments is critical to improve survival.

Consensus recommendations in the management of Ewing sarcoma from the National Ewing Sarcoma Tumor Board.

Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. Despite an international coordinated approach, several nuances, discrepancies, and debates remain in defining the standard of care for treating ES. In this review, the authors leverage the expertise assembled by formation of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of ES. This report is focused on select topics that apply to the management of patients with newly diagnosed ES. The specific topics covered include indications for bone marrow aspirate and biopsy for initial evaluation compared with fluorodeoxyglucose-positron emission tomography, the role of interval compressed chemotherapy in patients aged 18 years and older, the role of adding ifosfamide/etoposide to vincristine/doxorubicin/cyclophosphamide for patients with metastatic disease, the data on and role of high-dose chemotherapy with autologous stem cell transplantation, maintenance therapy, and whole-lung irradiation. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, the guidelines are intended to provide clarity and recommendations for the upfront management of patients with ES. PLAIN LANGUAGE SUMMARY: Ewing sarcoma is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. For this review, the authors used the experience of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of Ewing sarcoma. Although not intended to replace the clinical judgement of treating physicians, the guidelines will focus on the development of consensus statements for the upfront management of patients with Ewing sarcoma.

The role of ethicists in pediatric hematology/oncology: Current status and future needs.

As pediatric hematology/oncology (PHO) becomes more complex and sub-subspecialized, dedicated PHO ethicists have emerged as sub-subspecialists focused on addressing ethical issues encountered in clinical and research practices. PHO physicians and other clinicians with advanced training in bioethics contribute to the field through ethics research, education, and ethics consultation services. Furthermore, there exists a newer generation of PHO trainees interested in bioethics. This review details the experiences of current PHO ethicists, providing a blueprint for future educational, research and service activities to strengthen the trajectory of the burgeoning sub-subspecialty of PHO ethics. Creating an American Society of Pediatric Hematology/Oncology (ASPHO) ethics Special Interest Group, enhancing clinical ethics education for pediatric hematologists/oncologists (PHOs), developing multi-institutional research collaborations, and increasing attention to ethical issues germane to nonmalignant hematology will serve the interests of the entire field of PHO, enhancing the care of PHO patients and careers of PHOs.

Distance to treatment center is associated with survival in children and young adults with acute lymphoblastic leukemia.

BACKGROUND: Socioeconomic and demographic categories such as income, race, insurance status, and treatment center type are associated with outcomes in acute leukemia. This study was aimed at determining whether the distance to treatment center affects overall survival for children and young adults with acute leukemia. METHODS: The National Cancer Database was queried for patients 39 years old or younger who were diagnosed with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). A backward elimination procedure was used to select final multivariate Cox models. RESULTS: In total, 12,301 patients with AML and 22,683 patients with ALL were analyzed. The ALL model included distance to treatment center, Charlson-Deyo score, age, race, insurance status, and community income level. US census definitions of urban and rural were not statistically significant, and no interaction was significant for included variables. Compared with distances > 50 miles, all other distances were associated with improved survival (hazard ratio [HR] for ≤10 miles, 0.91; P = .04; HR for >10 to ≤20 miles, 0.86; P = .004; HR for >20 to ≤50 miles, 0.87; P = .005). The final model for AML included the same variables as the ALL model except for distance to treatment center, which was not statistically significant. CONCLUSIONS: For children and young adults with ALL, distances > 50 miles are associated with inferior overall survival; however, no difference is seen for AML. Although it is unknown whether differences in survival for patients with ALL based on distance are driven by relapse or treatment-related mortality, increased attention to adherence, supportive care, and logistics for patients traveling long distances is warranted. LAY SUMMARY: For children and young adults with acute lymphoblastic leukemia, living more than 50 miles from the treatment center is associated with worse outcomes.

Estimating cancer treatment intensity from SEER cancer registry data: methods and implications for population-based registry studies of pediatric cancers.

OBJECTIVE: The Intensity of Treatment Rating (ITR) Scale condenses treatment and clinical characteristics into a single measure to study treatment effects on downstream health outcomes across cancer types. This rating was originally developed for clinicians to determine from medical charts. However, large studies are often unable to access medical charts for all study participants. We developed and tested a method of estimating treatment intensity (TI) using cancer registry and patient self-reported data. METHODS: We estimated two versions of TI for a cohort of pediatric cancer survivors-one utilized information solely available from cancer registry variables (TIR) and the other included registry and self-reported information (TIS) from survey participants. In a subset of cases (n = 135) for whom the gold standard TI (TIC) was known, both TIR and TIS were compared to TIC by calculating percent agreement and weighted Cohen's kappa, overall and within cancer subtypes. RESULTS: In comparison to TIC, 71% of TI scores from both methods were in agreement (k = 0.61 TIR/0.54 TIS). Among subgroups, agreement ranged from lowest (46% TIR/39% TIS) for non-defined tumors (e.g., "Tumor-other"), to highest (94% TIR/94% TIS) for acute lymphoblastic leukemia (ALL). CONCLUSIONS: We developed a methodology to estimate TI for pediatric cancer research when medical chart review is not possible. High reliability was observed for ALL, the most common pediatric cancer. Additional validation is needed among a larger sample of other cancer subgroups. The ability to estimate TI from cancer registry data would assist with monitoring effects of treatment during survivorship in registry-based epidemiological studies.

Assessment of provider perspectives on otoprotection research for children and adolescents: A Children's Oncology Group Cancer Control and Supportive Care Committee survey.

BACKGROUND: Cisplatin-induced hearing loss (CIHL) is a common and debilitating toxicity for childhood cancer survivors. Understanding provider perspectives is crucial to developing otoprotection studies that are both informative and feasible. Two international trials (ACCL0431 and SIOPEL6) investigated the drug sodium thiosulfate (STS) as an otoprotectant, but definitive interpretation of the findings of these trials has been challenging. Adoption of STS has therefore been uneven, and provider perspectives on its role are unknown. PROCEDURE: The Children's Oncology Group (COG) Cancer Control and Supportive Care Neurotoxicity Subcommittee therefore conducted a survey of providers at COG institutions to determine perspectives on pediatric otoprotection practices and research surrounding three major themes: (1) prevalence of routine use of STS with cisplatin-based regimens, (2) application of audiometry to cisplatin therapy, and (3) preferred modalities for otoprotection research. RESULTS: Survey respondents (45%, 44/98 surveyed institutions) were of diverse institutional sizes, practice settings, and geographical locations primarily in the United States and Canada. Overall, respondents considered CIHL an important toxicity and indicated strong enthusiasm for future studies (98%, 40/41). Results indicated that while STS was the current or planned standard of care in a minority of responding institutions (36%, 16/44), most sites were receptive to its inclusion in appropriate study designs. Application of audiometry for ototoxicity monitoring varied widely across sites. For otoprotection research, systemic agents were preferred (68%, 28/41) as compared with intratympanic approaches. CONCLUSION: These results suggest that pediatric otoprotection trials remain of interest to providers; the emphasis of these trials should remain on systemic and not intratympanic therapy.

A 10-Month-Old Infant Presenting With Signs of Precocious Puberty Secondary to a Sclerosing Stromal Tumor of the Ovary in the Absence of Hormonal Elevation.

Precocious puberty in an infant is an alarming and infrequent finding, making the differential diagnosis difficult for practitioners. Precocious puberty secondary to a sclerosing stromal tumor (SST) of the ovary is rare. We present a case of a child that began precocious puberty at 3 months of age including development of breast buds, pubic hair, growth spurt, and menarche 5 days prior to presenting to pediatric endocrinology at 10 months. She underwent right salpingo-oophorectomy which demonstrated a soft tissue mass occupying almost the entire ovary with a tan-pink fleshy cut surface. Histological examination confirmed a variant of SST. This case represents an extremely young onset of precocious puberty secondary to a variant of SST without hormonal elevation.

A prospective comparison of cancer clinical trial availability and enrollment among adolescents/young adults treated at an adult cancer hospital or affiliated children's hospital.

BACKGROUND: Low cancer clinical trial (CCT) enrollment may contribute to survival disparities affecting adolescents and young adults (AYAs) (ages 15-39 years). The objective of this study was to evaluate whether differences in CCT availability related to treatment site could explain the low CCT enrollment. METHODS: This prospective, observational cohort study was conducted at an academic children's hospital and its affiliated but geographically separated adult cancer hospital within a National Cancer Institute-designated Comprehensive Cancer Center. For consecutive, newly diagnosed AYA patients, it was determined whether an appropriate CCT existed nationally, was available at the treatment site, and was used for enrollment. Proportions of AYAs in these categories were compared between sites using the chi-square test. RESULTS: One hundred fifty-two consecutive AYA patients were included from the children's hospital (n = 68; ages 15-20 years) and the adult cancer hospital (n = 84; ages 18-39 years). Although there was no difference in CCT existence for individual AYA patients by site (children's hospital [36 of 68 patients; 52.9%] vs adult cancer hospital [45 of 84 patients; 53.6%]; P = .938), CCT availability was significantly lower at the adult cancer hospital (14 of 84 patients [16.7%] vs 30 of 68 [44.1%] at the children's hospital; P < .001). The proportion of AYAs enrolled was low at both sites (8 of 68 patients [11.8%] vs 6 of 84 patients [7.1%], respectively; P = .327). Fewer existing CCTs were available at the adult cancer hospital (4 of 27 patients [14.8%] vs 8 of 14 patients [57.1%], respectively), and those were directed toward solid tumors and new agents. CONCLUSIONS: Efforts to improve low CCT enrollment among AYAs should be differentiated by treatment site. In the adult setting, these efforts should be aimed at improving CCT availability by overcoming site-level barriers to opening existing CCTs.

A prospective, observational cohort study comparing cancer clinical trial availability and enrollment between early adolescents/young adults and children.

BACKGROUND: Poor enrollment of adolescents and young adults (AYAs) (ages 15-39 years) onto cancer clinical trials (CCTs) may contribute to inferior survival gains compared with children. In this study, the authors assessed whether differences in CCT availability would explain lower CCT enrollment for early AYAs (eAYAs) (ages 15-21 years). METHODS: This prospective, observational cohort study was conducted at a single academic children's hospital. For consecutive patients who were newly diagnosed with cancer over a 13-month period, it was determined whether an appropriate CCT existed nationally or was available locally and whether enrollment on that CCT occurred. The proportions of eAYAs versus children in each category were compared using the chi-square test. The impact of age and other factors on enrollment status was assessed using logistic regression analysis. RESULTS: Among 216 patients, 58 were eAYAs, and 158 were children. There was no difference in the proportion of eAYAs versus children who had an existing CCT (28 of 58 eAYAs [48.3%] vs 85 of 158 children [53.8%]; P = .47) or an available CCT (23 of 58 eAYAs [39.7%] vs 75 of 158 children [47.5%]; P = .31). However, significantly fewer eAYAs were enrolled when a CCT was available (7 of 23 eAYAs [30.4%] vs 50 of 75 children [67.7%]; P = .002). In multivariable analysis, eAYAs were significantly less likely than children to be enrolled in an available CCT (adjusted odds ratio, 0.22; 95% confidence interval, 0.08-0.62). CONCLUSIONS: Equal proportions of children and eAYAs had CCTs available, but significantly fewer eAYAs were enrolled. These findings suggest that, for eAYAs, factors other than CCT availability are important enrollment barriers and should be addressed. Cancer 2018;124:983-90. © 2017 American Cancer Society.

Prevalence and correlates of health information-seeking among Hispanic and non-Hispanic childhood cancer survivors.

PURPOSE: Childhood cancer survivors (CCS) report high unmet information needs. This study examined the prevalence of cancer-related information-seeking among CCS and investigated associations between information-seeking behavior and positive health outcomes such as follow-up care. METHODS: Participants (n = 193) were young adult CCS diagnosed with cancer in Los Angeles County, 54% of Hispanic ethnicity, with a mean age of 19.87, in remission, and at least 2 years from completion of treatment. CCS were asked where they accessed health information related to their cancer with response options categorized into four information domains: hospital resources, social media, other survivors, and family members. Multivariable logistic regression was used to assess variables associated with each information domain, including sociodemographics, post-traumatic growth (i.e., reporting positive changes since cancer diagnosis), health care engagement, level of education, and health insurance status. RESULTS: Hospital resources were the most commonly accessed information domain (65.3%), and CCS of Hispanic ethnicity (vs. non-Hispanic) were more likely to access this source. Seeking information from other cancer survivors was positively associated with follow-up care and post-traumatic growth. Hispanic CCS were marginally less likely to seek information from other survivors and family than non-Hispanics. CONCLUSIONS: While CCS obtain information from a variety of sources, hospital resources are an important site for access, particularly for individuals of Hispanic ethnicity. Information sharing between survivors may promote positive health care engagement; however, Hispanic CCS may be less likely to utilize this resource and may face barriers in information sharing with other cancer survivors.

Balloon Kyphoplasty for Managing Intractable Pain in Pediatric Pathologic Vertebral Fractures.

BACKGROUND: Vertebral compression fractures are a common result of osteoporosis and osteopenia secondary to steroid use and chemotherapy treatment. Balloon kyphoplasty is a treatment option with good to excellent results well described in adults. Although a few recent studies have been published regarding the use of kyphoplasty in children, no formal indication exists for the pediatric population. The purpose of this study is to describe the outcomes of 3 chronically ill children with intractable pain from vertebral compression fractures, managed with kyphoplasty. METHODS: We retrospectively reviewed 3 pediatric patients who underwent balloon kyphoplasty for vertebral compression fractures secondary to chronic illness. Patient variables included age, sex, primary diagnosis and treatments, levels of vertebral fracture, and time elapsed from initial therapy to fracture. A numeric rating scale of 0 to 10 was used for patient-reported pain, before and after kyphoplasty. Preoperative and postoperative analgesic use and physical function were also described. Surgical variables included levels of kyphoplasty, operative time, and procedure-related complications. RESULTS: The primary diagnoses were relapsed rhabdomyosarcoma, abdominal desmoplastic small round cell tumor, and IPEX-like (immune dysregulation, polyendrocrinopathy, enteropathy, X-linked) syndrome. All 3 patients were males, aged 12, 12, and 13, respectively, at the time of kyphoplasty. Pain scores were 8 to 9 preoperatively in 2 patients, severely affecting their physical function including independent walking. Excruciating back pain was a contributing factor to the respiratory distress of the third patient, who required elective intubation. All of the patients reported significant pain relief (range, 0 to 2) and improved physical function with kyphoplasty. The third patient was successfully extubated 1 week postoperatively and eventually returned to baseline activity. There were no complications related to kyphoplasty. CONCLUSIONS: Balloon kyphoplasty seems to be safe in terminally ill children and may be a useful tool for managing intractable pain due to vertebral compression fractures. LEVEL OF EVIDENCE: Level IV-retrospective case series.

Not just little adults: a review of 102 paediatric ethics consultations.

AIM: The American Academy of Pediatrics statement on institutional ethics committees highlights the importance of paediatric ethics consultation. However, little has been published on actual experience with ethics consultation in paediatrics. The objective of this study was to review and describe topics covered by a large retrospective sample of clinical ethics consultations in paediatric medicine. METHODS: We reviewed ethics consultations involving patients of <18 years of age from January 2005 to July 2013 at one institution. Descriptive statistics of the patient population, the reason for the ethics consultation and the consultant's perceived contribution to the case were generated. Subgroups of patients were compared based on demographic and clinical characteristics using Wilcoxon's rank sum tests, chi-square tests and logistic regression models. RESULTS: Most of the 102 eligible consultations originated from intensive care units and were requested by attending physicians. The most frequent topic leading to consultation was end-of-life issues. Both younger age and male sex were associated with consults for end-of-life issues (p < 0.001 and p = 0.010). CONCLUSION: This analysis provides important information describing the type of consults requested in paediatric medicine, which is necessary given the movement towards professionalising clinical ethics consultation. Further empirical research is needed on ethics consultation in paediatrics.

Creation of a quality improvement collaborative to address adolescent and young adult cancer clinical trial enrollment: ATAQI (AYA trial access quality initiative).

Adolescent and young adult (AYA) participation in cancer clinical trials (CCTs) is suboptimal, hindering further improvements in survival, quality of life, and basic understanding of cancer pathophysiology in this population. Prior studies have identified barriers and facilitators to AYA CCT enrollment; however, few interventional studies have attempted to address these barriers and measure tangible changes. In September 2020, a task force was established to address CCT enrollment barriers at a multi-institutional level utilizing a quality improvement collaborative model for improvement. The AYA Trial Access Quality Initiative was developed with the goal of bring multidisciplinary teams together across multiple sites to learn, apply and share their methods of improvement. It uses a structured process of learning sessions lead by quality improvement and clinical experts who help facilitate learning and problem solving which are followed by action phases. During the pilot phase of the collaboration, one key driver of CCT enrollment in AYA's will be addressed: communication between adult and pediatric oncology by implementation of various interventions at sites. The number of AYAs screened for and enrolled on CCTs will be tracked over the course of the collaborative along with the process measures. It is expected that the interventions will promote engagement of stakeholders in the process of screening AYA oncology patients for eligibility on CCTs. This will hopefully create a favorable environment conducive for increasing enrollment on CCTs and lead to the development of a system-wide quality improvement framework to improve AYA CCT enrollment.

Substance Use Among Young Adult Survivors of Childhood Cancer With Cognitive Impairment: An Analysis of the Project Forward Cohort.

PURPOSE: Young adult childhood cancer survivors (YACCSs) are often impacted by cancer-related cognitive impairment (CRCI) and psychological distress. Using the Project Forward Cohort, we evaluated the relationship between CRCI and substance use behaviors. METHODS: YACCSs were surveyed between 2015 and 2018 (N = 1,106, female = 50.8%, Hispanic = 51.5%, median age = 25.5 years). Associations between CRCI and substance use (tobacco, binge drinking, marijuana, prescription drug misuse, and e-cigarette/vaporizer) were examined in multivariate logistic or log-binomial regressions, adjusting for child at diagnosis (0-14 years), years since diagnosis, sex, race/ethnicity, cancer type, and treatment intensity. Mediation analysis was performed to determine opportunities for interventions. RESULTS: CRCI was reported by 144 (13.0%) survivors. The highest prevalence was observed in CNS cancers (25.4%) and leukemia (13.3%) survivors. After covariate adjustment, CRCI was associated with 2.26 times the odds of prior 30-day vaping (95% CI, 1.24 to 4.11; P = .007). Mediators with significant indirect effects in the CRCI-vaping relationship include depressive symptoms (Center for Epidemiological Studies Depression Scale) and having two or more cancer-related late effects (P < .05). CONCLUSION: CRCI among YACCSs was associated with reports of vaping. Oncologists should screen for vaping behavior if CRCI is apparent. Increasing access to long-term follow-up clinics, addressing physical and mental health issues, and monitoring and educating on vaping and other substance use behaviors is recommended to improve the long-term health of YACCSs.

Clinical Trial Participation: A Qualitative Study of Adolescents and Younger Adults Recently Diagnosed with Cancer.

Purpose: Although participation of adolescents and young adults (AYAs) in cancer clinical trials (CCTs, i.e., cancer-directed treatment studies) is low, their decision-making perspectives are not well understood, especially following recent diagnosis. Methods: Semistructured interviews with younger AYAs (15-21 years old) eligible for a CCT were to be held within 60 days of beginning treatment at Children's Hospital Los Angeles, an academic pediatric hospital. Using grounded theory methods, key themes regarding CCT participation, barriers, and facilitators were identified from interview transcripts. Thematic saturation was confirmed. Results: Of nine participants, three were <18 years old, four Hispanic, six male, six diagnosed with leukemia, eight enrolled in a CCT, and eight also enrolled in ancillary studies. Four overarching themes emerged: (1) Initial Consent encompassed the first discussion of CCT with patients reflecting positive and negative effects of timing, decisional role, and the emotional impact following cancer diagnosis; (2) Informing Participation involved decision-making processes, specific knowledge, comprehension, and external influences; (3) Participant Relationships emphasized the importance of communication and relationships with providers and parents; and (4) Patient Determinants centered on motives from different perspectives, pre-conceived attitudes, and understanding of CCTs. Conclusion: Recommendations for improving CCT participation among younger AYAs include separating the diagnosis/treatment and CCT discussions, assigning AYAs a meaningful decisional role, having ongoing provider conversations, designing trials to minimize burden, and developing age-appropriate decision aids.

Neutrophil to Lymphocyte Ratio (NTLR) Predicts Local Control Failure and Overall Survival after Stereotactic Body Radiotherapy (SBRT) In Metastatic Sarcoma.

The neutrophil to lymphocyte ratio (NTLR) and absolute lymphocyte count (ALC) recovery are prognostic across many cancers. We investigated whether NLTR predicts SBRT success or survival in a metastatic sarcoma cohort treated with SBRT from 2014 and 2020 (N = 42). Wilcox Signed Rank Test and Friedman Test compare NTLR changes with local failure vs. local control (N = 138 lesions). Cox analyses identified factors associated with overall survival. If local control was successful, NLTR change was not significant (p = 0.30). However, NLTR significantly changed in patients local failure (p = 0.027). The multivariable Cox model demonstrated higher NLTR before SBRT was associated with worse overall survival (p = 0.002). The optimal NTLR cut point was 5 (Youden index: 0.418). One-year overall survival in SBRT metastatic sarcoma cohort was 47.6% (CI 34.3%-66.1%). Patients with an NTLR above 5 had a one-year overall survival of 37.7% (21.4%-66.3%); patients with an NTLR below 5 had a significantly improved overall survival of 63% (43.3%-91.6%, p = 0.014). Since NTLR at the time of SBRT was significantly associated with local control success and overall survival in metastatic sarcoma treated with SBRT, future efforts to reduce tumor inhibitory microenvironment factors and improved lymphocyte recovery should be investigated.

Neutrophil to lymphocyte ratio (NTLR) predicts local control and overall survival after stereotactic body radiotherapy (SBRT) in metastatic sarcoma.

The neutrophil to lymphocyte ratio (NTLR) and absolute lymphocyte count (ALC) recovery are prognostic across many cancers. We investigated whether NLTR predicts SBRT success or survival in a metastatic sarcoma cohort treated with SBRT from 2014 and 2020 (N = 42). Wilcox Signed Rank Test and Friedman Test compare NTLR changes with local failure vs. local control (N = 138 lesions). Cox analyses identified factors associated with overall survival. If local control was successful, NLTR change was not significant (p = 0.30). However, NLTR significantly changed in patients with local failure (p = 0.027). The multivariable Cox model demonstrated higher NLTR before SBRT was associated with worse overall survival (p = 0.002). The optimal NTLR cut point was 5 (Youden index: 0.418). One-year overall survival in SBRT metastatic sarcoma cohort was 47.6% (CI 34.3%-66.1%). Patients with an NTLR above 5 had a one-year overall survival of 37.7% (21.4%-66.3%); patients with an NTLR below 5 had a significantly improved overall survival of 63% (43.3%-91.6%, p = 0.014). Since NTLR at the time of SBRT was significantly associated with local control success and overall survival in metastatic sarcoma treated with SBRT, future efforts to reduce tumor inhibitory microenvironment factors and improve lymphocyte recovery should be investigated.

Association between biologically effective dose and local control after stereotactic body radiotherapy for metastatic sarcoma.

Introduction: Stereotactic body radiation therapy (SBRT) is increasingly utilized for patients with recurrent and metastatic sarcoma. SBRT affords the potential to overcome the relative radioresistance of sarcomas through delivery of a focused high biological effective dose (BED) as an alternative to invasive surgery. We report local control outcomes after metastatic sarcoma SBRT based on radiation dose and histology. Methods: From our IRB-approved single-institution registry, all patients treated with SBRT for metastatic sarcoma between 2014 and 2020 were identified. Kaplan-Meier analysis was used to estimate local control and overall survival at 1 and 2 years. A receiver operating characteristic (ROC) curve was generated to determine optimal BED using an α/ß ratio of 3. Local control was compared by SBRT dose using the BED cut point and evaluated by histology. Results: Forty-two patients with a total of 138 lesions met inclusion criteria. Median imaging follow up was 7.73 months (range 0.5-35.0). Patients were heavily pre-treated with systemic therapy. Median SBRT prescription was 116.70 Gy BED (range 66.70-419.30). Desmoplastic small round cell tumor, Ewing sarcoma, rhabdomyosarcoma, and small round blue cell sarcomas were classified as radiosensitive (n = 63), and all other histologies were classified as radioresistant (n = 75). Local control for all lesions was 66.7% (95% CI, 56.6-78.5) at 1 year and 50.2% (95% CI, 38.2-66.1) at 2 years. Stratifying by histology, 1- and 2-year local control rates were 65.3% and 55.0%, respectively, for radiosensitive, and 68.6% and 44.5%, respectively, for radioresistant histologies (p = 0.49). The ROC cut point for BED was 95 Gy. Local control rates at 1- and 2-years were 75% and 61.6%, respectively, for lesions receiving >95 Gy BED, and 46.2% and 0%, respectively, for lesions receiving <95 Gy BED (p = 0.01). On subgroup analysis, local control by BED > 95 Gy was significant for radiosensitive histologies (p = 0.013), and trended toward significance for radioresistant histologies (p = 0.25). Conclusion: There is a significant local control benefit for sarcoma SBRT when a BED > 95 Gy is used. Further investigation into the dose-response relationship is warranted to maximize the therapeutic index.