Management of chordoma and chondrosarcoma with definitive dose-escalated single-fraction spine stereotactic radiosurgery.

PURPOSE: The management of chordoma or chondrosarcoma involving the spine is often challenging due to adjacent critical structures and tumor radioresistance. Spine stereotactic radiosurgery (SSRS) has radiobiologic advantages compared with conventional radiotherapy, though there is limited evidence on SSRS in this population. We sought to characterize the long-term local control (LC) of patients treated with SSRS. METHODS: We retrospectively reviewed patients with chordoma or chondrosarcoma treated with dose-escalated SSRS, defined as 24 Gy in 1 fraction to the gross tumor volume. Overall survival (OS) was calculated by Kaplan-Meier functions. Competing risk analysis using the cause-specific hazard function estimated LC time. RESULTS: Fifteen patients, including 12 with chordoma and 3 with chondrosarcoma, with 22 lesions were included. SSRS intent was definitive, single-modality in 95% of cases (N = 21) and post-operative in 1 case (5%). After a median censored follow-up time of 5 years (IQR 4 to 8 years), median LC time was not reached (IQR 8 years to not reached), with LC rates of 100%, 100%, and 90% at 1 year, 2 years, and 5 years. The median OS was 8 years (IQR 3 years to not reached). Late grade 3 toxicity occurred after 23% of treatments (N = 5, fracture), all of which were managed successfully with stabilization. CONCLUSION: Definitive dose-escalated SSRS to 24 Gy in 1 fraction appears to be a safe and effective treatment for achieving durable local control in chordoma or chondrosarcoma involving the spine, and may hold particular importance as a low-morbidity alternative to surgery in selected cases.

Prognostic factors for pediatric, adolescent, and young adult patients with non-DIPG grade 4 gliomas: a contemporary pooled institutional experience.

PURPOSE: WHO grade 4 gliomas are rare in the pediatric and adolescent and young adult (AYA) population. We evaluated prognostic factors and outcomes in the pediatric versus AYA population. METHODS: This retrospective pooled study included patients less than 30 years old (yo) with grade 4 gliomas treated with modern surgery and radiotherapy. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analysis. RESULTS: Ninety-seven patients met criteria with median age 23.9 yo at diagnosis. Seventy-seven patients were ≥ 15 yo (79%) and 20 patients were < 15 yo (21%). Most had biopsy-proven glioblastoma (91%); the remainder had H3 K27M-altered diffuse midline glioma (DMG; 9%). All patients received surgery and radiotherapy. Median PFS and OS were 20.9 months and 79.4 months, respectively. Gross total resection (GTR) was associated with better PFS in multivariate analysis [HR 2.00 (1.01-3.62), p = 0.023]. Age ≥ 15 yo was associated with improved OS [HR 0.36 (0.16-0.81), p = 0.014] while female gender [HR 2.12 (1.08-4.16), p = 0.03] and DMG histology [HR 2.79 (1.11-7.02), p = 0.029] were associated with worse OS. Only 7% of patients experienced grade 2 toxicity. 62% of patients experienced tumor progression (28% local, 34% distant). Analysis of salvage treatment found that second surgery and systemic therapy significantly improved survival. CONCLUSION: Age is a significant prognostic factor in WHO grade 4 glioma, which may reflect age-related molecular alterations in the tumor. DMG was associated with worse OS than glioblastoma. Reoperation and systemic therapy significantly increased survival after disease progression. Prospective studies in this population are warranted.

Harmonica consensus, controversies, and future directions in radiotherapy for pediatric Wilms tumors.

Radiotherapy (RT) is essential for multimodality treatment of pediatric renal tumors, particularly in higher-risk and metastatic disease. Despite decades of use, particularly for Wilms tumor, there remain controversies regarding RT indications, timing, dose, and targets. To align global management, we address these issues in this international HARMONIsation and CollAboration (HARMONICA) project. There are multiple knowledge gaps and opportunities for future research including: (1) utilization of advanced RT technologies, including intensity-modulated RT, proton beam therapy, combined with image-guided RT to reduce target volumes; (2) impact of molecular biomarkers including loss of heterozygosity at 1p, 16q, and 1q gain on RT indications; (3) mitigation of reproductive toxicity following RT; (4) promotion of RT late effects research; and (5) support to overcome challenges in RT utilization in low- and middle-income countries where 90% of the world's children reside. Here, we outline current status and future directions for RT in pediatric renal tumors.

Renal function in abdominal neuroblastoma patients undergoing proton radiotherapy.

BACKGROUND: The purpose of this study is to analyze renal function outcomes in abdominal neuroblastoma patients undergoing proton therapy (PT). PROCEDURE: From 2011 to 2019, two single-institution Institutional Review Board-approved protocols prospectively enrolled neuroblastoma patients for data collection. To assess renal function, serum creatinine (Cr), blood urea nitrogen (BUN), and creatinine clearance (CrCl) before proton therapy (pre-PT) were compared with the values at last follow-up. RESULTS: A total of 30 children with abdominal neuroblastoma with median age 3.5 years (range, 0.9-9.1) at time of PT were included in this study. All patients underwent chemotherapy and resection of primary tumor prior to PT. Two patients required radical nephrectomy. Median follow-up after PT was 35 months. Mean dose to ipsilateral and contralateral kidney was 13.9 and 5.4 Gy, respectively. No patients developed hypertension or renal dysfunction during follow-up. There was no statistically significant change in serum BUN (p = .508), CrCl (p = .280), or eGFR (p = .246) between pre-PT and last follow-up. CONCLUSION: At a median follow-up of almost 3 years, renal toxicity was uncommon after PT. Longer follow-up and larger patient cohort data are needed to further assess impact of PT on renal function in this population.

Overall survival and secondary malignant neoplasms in children receiving passively scattered proton or photon craniospinal irradiation for medulloblastoma.

BACKGROUND: Both intensity-modulated radiotherapy (RT) and passively scattered proton therapy have a risk of secondary malignant neoplasm (SMN) in children. To determine the influence of RT modality on the incidence of SMN after craniospinal irradiation (CSI), the authors compared the incidence of SMN in children who had medulloblastoma treated with either photon CSI plus an intensity-modulated RT boost (group I) or passively scattered proton CSI plus a boost (group II). METHODS: From 1996 to 2014, 115 children with medulloblastoma (group I, n = 63; group II, n = 52) received CSI followed by a boost to the tumor bed. Most patients had standard-risk disease (63.5%). The median follow-up was 12.8 years for group I and 8.7 years for group II. RESULTS: The 5-year and 10-year overall survival (OS) rates were 88.8% and 85.1%, respectively, for standard-risk patients and 63.1% and 57.3%, respectively, for high-risk patients, with no OS difference by RT modality (P = .81). Six SMNs were identified (4 in group I, 2 in group II). The 5-year and 10-year SMN incidence rates were 1.0% and 6.9%, respectively (0.0% and 8.0%, respectively, in group I; 2.2% and 4.9%, respectively, in group II; P = .74). Two SMNs occurred in the clinical target volume in the brain, 2 occurred in the exit dose region from the photon spinal field, 1 occurred in the entrance path of a proton beam, and 1 occurred outside the radiation field. There were no reported cases of secondary leukemia. CONCLUSIONS: This analysis demonstrates no difference in OS or SMN incidence between patients in groups I and II 10 years after RT. LAY SUMMARY: One hundred fifteen children with medulloblastoma received radiotherapy (RT) with either photon craniospinal irradiation (CSI) and an intensity-modulated RT boost (group I; n = 63) or passively scattered proton CSI and a boost (group II;, n = 52). The majority of children had standard-risk disease (63.5%). The 5-year and 10-year overall survival rates were 88.8% and 85.1% for standard-risk patients, respectively, and 63.1% and 57.3% for high-risk patients, respectively, with no difference in overall survival by RT group (P = .81). The 5-year and 10-year second malignant neoplasm incidence rates were 1.0% and 6.9%, respectively, with no difference in second malignant neoplasm incidence according to RT group (P = .74).

Early radiotherapy preserves vision in sporadic optic pathway glioma.

BACKGROUND: Sporadic optic pathway/hypothalamic gliomas represent a unique entity within pediatric low-grade glioma. Despite favorable survival, location makes treatment difficult and local progression debilitating. This study is a longitudinal assessment of visual acuity (VA) among children treated within the last 2 decades. METHODS: Clinical characteristics were abstracted for patients treated from 2000 to 2018 at Texas Children's Cancer Center in Houston. Ophthalmologic data taken at 3- to 6-month intervals were examined with age-appropriate VA metrics converted to the LogMAR (logarithm of the minimum angle of resolution) scale. Kaplan-Meier blindness-free survival (BFS) curves, calculated as time-to-bilateral functional blindness (LogMAR ≥0.8 in both eyes), were calculated for patients receiving early radiation therapy (RT; upfront or as first-line salvage treatment) or chemotherapy (CT) and evaluated using the log-rank test. RESULTS: Thirty-eight patients with a median follow-up of 8.5 years (range, 2-17 years) were identified. Median age at diagnosis was 3 years (interquartile range, <1-6 years). Early RT was administered in 11 patients (29%). Twenty-seven patients (71%) were treated primarily with CT, initiated at a median age of 3.5 years (range, <1-11 years). Eight patients in the CT group did eventually require RT secondary to VA loss and following multiple lines of CT. Median age at RT for all patients was 11 years (range, 3-17 years). BFS rates were 81% at 5 years and 60% at 8 years for CT and 100% at 5 and 8 years for early RT (P = .017). CONCLUSIONS: In a contemporary cohort, early RT, defined as initial or first-line salvage therapy, was found to have superior BFS for appropriately selected patients with sporadic optic pathway/hypothalamic gliomas. LAY SUMMARY: Children with low-grade brain tumors of the optic pathway generally have excellent long-term survival; however, given the location of these tumors, there can commonly be threatened vision if the tumor grows. Although radiation is generally deferred in children on the basis of legitimate concerns regarding the effects on the developing brain, it may represent a vision-preserving therapy for well-selected older patients.

Early and Midtreatment Mortality in Palliative Radiotherapy: Emphasizing Patient Selection in High-Quality End-of-Life Care.

BACKGROUND: Palliative radiotherapy (RT) is effective, but some patients die during treatment or too soon afterward to experience benefit. This study investigates end-of-life RT patterns to inform shared decision-making and facilitate treatment consistent with palliative goals. MATERIALS AND METHODS: All patients who died ≤6 months after initiating palliative RT at an academic cancer center between 2015 and 2018 were identified. Associations with time-to-death, early mortality (≤30 days), and midtreatment mortality were analyzed. RESULTS: In total, 1,620 patients died ≤6 months from palliative RT initiation, including 574 (34%) deaths at ≤30 days and 222 (14%) midtreatment. Median survival was 43 days from RT start (95% CI, 41-45) and varied by site (P<.001), ranging from 36 (head and neck) to 53 days (dermal/soft tissue). On multivariable analysis, earlier time-to-death was associated with osseous (hazard ratio [HR], 1.33; P<.001) and head and neck (HR, 1.45; P<.001) sites, multiple RT courses ≤6 months (HR, 1.65; P<.001), and multisite treatments (HR, 1.40; P=.008), whereas stereotactic technique (HR, 0.77; P<.001) and more recent treatment year (HR, 0.82; P<.001) were associated with longer survival. No difference in time to death was noted among patients prescribed conventional RT in 1 to 10 versus >10 fractions (median, 40 vs 47 days; P=.272), although the latter entailed longer courses. The 30-day mortality group included 335 (58%) inpatients, who were 27% more likely to die midtreatment (P=.031). On multivariable analysis, midtreatment mortality among these inpatients was associated with thoracic (odds ratio [OR], 2.95; P=.002) and central nervous system (CNS; OR, 2.44; P=.002) indications, >5-fraction courses (OR, 3.27; P<.001), and performance status of 3 to 4 (OR, 1.63; P=.050). Conversely, palliative/supportive care consultation was associated with decreased midtreatment mortality (OR, 0.60; P=.045). CONCLUSIONS: Earlier referrals and hypofractionated courses (≤5-10 treatments) should be routinely considered for palliative RT indications, given the short life expectancies of patients at this stage in their disease course. Providers should exercise caution for emergent thoracic and CNS indications among inpatients with poor prognoses due to high midtreatment mortality.

Relationship between treatment center case volume and survival for localized Ewing sarcoma: The role of radiotherapy timing.

In the treatment of localized Ewing sarcoma (EWS), delays in local therapy are known to adversely impact overall survival (OS). However, the role of treatment center volume in EWS outcomes, and the interaction between center volume and local therapy timing with definitive radiotherapy, remains unknown. Using the National Cancer Database, we demonstrate that treatment at the lowest EWS volume centers is associated with reduced OS, explained partly by higher rates of delayed local therapy. Treatment at the highest volume centers results in improved OS, but appears independent of radiotherapy timing. Future efforts to improve care for EWS patients across treatment centers are imperative.

Treatment strategies for glioblastoma in older patients: age is just a number.

BACKGROUND/PURPOSE: Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in many clinical trials (including EORTC 22,981) as well as their historically poor overall survival. METHODS: A retrospective chart review was conducted at a single high-volume cancer center for newly diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. RESULTS: A total of 158 newly diagnosed GBM patients aged 65 years and older were identified. One hundred forty-four patients (91.1%) received radiotherapy (RT) and 130 patients (90.3%) received concurrent temozolomide with RT. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temozolomide. 23% of patients discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. With a median follow-up time of 35.0 months, median overall survival (OS) time for the full cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p = 0.002, HR 0.46; 95% CI 0.63-0.82), completing planned RT course (p = 0.01, HR 0.29; 95% CI 0.11-0.75), and completing 6 cycles of adjuvant temozolomide (p = 0.01, HR 2.62; 95% CI 1.67-4.12) were independently associated with improved OS. CONCLUSIONS: Our cohort of elderly GBM patients was predominantly treated with standard of care therapy based on EORTC 22,981. Despite their age, these patients generally tolerated treatment well and had favorable outcomes compared to those reported for patients treated on EORTC 22,981. Based on these findings, using advanced age as the basis for treatment de-escalation or as an exclusionary criterion in clinical trials should be discouraged.

Efficacy of proton therapy in children with high-risk and locally recurrent neuroblastoma.

PURPOSE: Proton therapy is currently used in the management of pediatric tumors to decrease late toxicities. However, one of the criticisms of proton therapy is the limited data regarding efficacy on disease control. The purpose of this study was to examine local and distant control rates after proton therapy for neuroblastoma. METHODS AND MATERIALS: Eighteen patients with high-risk (n = 16) and locally recurrent neuroblastoma (n = 2) were treated with curative intent and received proton therapy to the primary site and up to three post-induction MIBG-avid metastatic sites. Primary sites (n = 18) were treated to 21-36 Gy (relative biological effectiveness [RBE]), and metastatic sites (n = 16) were treated to 21-24 Gy (RBE). Local control and survival rates were calculated using the Kaplan-Meier method. RESULTS: With a median follow-up of 60.2 months, two- and five-year local control rates at the irradiated primary site were 94% and 87%, respectively. No failures at irradiated distant metastatic sites were observed. The five-year progression-free survival (PFS) was 64%, and the five-year overall survival (OS) was 94%. The extent of surgical resection was not associated with local control, PFS, or OS. No radiation-related nephropathy or hepatopathy was reported. CONCLUSIONS: Excellent local control was achieved using proton therapy to the primary and post-induction MIBG-positive distant sites. The predominant site of failure is progression in post-induction non-MIBG-avid distant sites. Although proton therapy provides high rates of local control with acceptable toxicity for neuroblastoma, further advances in systemic therapy are needed for the improved control of systemic disease.

Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trial.

BACKGROUND: After brain metastasis resection, whole brain radiotherapy decreases local recurrence, but might cause cognitive decline. We did this study to determine if stereotactic radiosurgery (SRS) to the surgical cavity improved time to local recurrence compared with that for surgical resection alone. METHODS: In this randomised, controlled, phase 3 trial, we recruited patients at a single tertiary cancer centre in the USA. Eligible patients were older than 3 years, had a Karnofsky Performance Score of 70 or higher, were able to have an MRI scan, and had a complete resection of one to three brain metastases (with a maximum diameter of the resection cavity ≤4 cm). Patients were randomly assigned (1:1) with a block size of four to either SRS of the resection cavity (within 30 days of surgery) or observation. Patients were stratified by histology of the primary tumour, metastatic tumour size, and number of metastases. The primary endpoint was time to local recurrence in the resection cavity, assessed by blinded central review of brain MRI scans by the study neuroradiologist in the modified intention-to-treat population that analysed patients by randomised allocation but excluded patients found ineligible after randomisation. Participants and other members of the treatment team (excluding the neuroradiologist) were not masked to treatment allocation. The trial is registered with ClinicalTrials.gov, number NCT00950001, and is closed to new participants. FINDINGS: Between Aug 13, 2009, and Feb 16, 2016, 132 patients were randomly assigned to the observation group (n=68) or SRS group (n=64), with 128 patients available for analysis; four patients were ineligible (three from the SRS group and one from the observation group). Median follow-up was 11·1 months (IQR 4·8-20·4). 12-month freedom from local recurrence was 43% (95% CI 31-59) in the observation group and 72% (60-87) in the SRS group (hazard ratio 0·46 [95% CI 0·24-0·88]; p=0·015). There were no adverse events or treatment-related deaths in either group. INTERPRETATION: SRS of the surgical cavity in patients who have had complete resection of one, two, or three brain metastases significantly lowers local recurrence compared with that noted for observation alone. Thus, the use of SRS after brain metastasis resection could be an alternative to whole-brain radiotherapy. FUNDING: National Institutes of Health.

Ewing sarcoma family of tumors in children younger than 10 years of age.

AIM: Few data exist regarding the clinical characteristics and outcome of young children with Ewing sarcoma family of tumors (ESFT). METHODS: We reviewed the records of ESFT patients at our institution younger than 10 years of age at diagnosis. RESULTS: Forty-two patients were identified. Median age was 6.4 years (range 0.6-9.5 years). Most patients had T2 (>5 cm) tumors (n = 31; 74%). Most common primary site was the extremity (n = 17; 41%). Seven patients (17%) had metastasis at diagnosis. For local tumor control, 20 patients had surgery only, 13 had radiation therapy only, and 6 had surgery plus radiation. Surgical margin status was negative in 19 patients (73%). Median follow-up was 4.7 years (range 0.7-29.7 years), and 5-year relapse-free survival (RFS) and overall survival (OS) estimates were 67% (95% CI: 53-84%) and 82% (95% CI: 71-95%), respectively. Metastasis at presentation was the only significant predictor for decreased RFS (P = 0.008) and OS (P = 0.01). A trend was seen for T2 tumors with worse OS (P = 0.09). CONCLUSION: Patients younger than 10 years of age with ESFT may have a better OS than older patients, but further study of a homogeneously treated larger cohort is needed.

Cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for children, adolescents, and young adults: the first 50 cases.

BACKGROUND: Extensive peritoneal metastatic disease is rare in children. Although usually manifested as carcinomatosis in adults, sarcomatosis is more common in children. The authors began a pediatric hyperthermic intraperitoneal chemotherapy (HIPEC) program, and this report describes their initial results from the first 50 pediatric, adolescent, and young adult patients. METHODS: A single-institution, retrospective study investigated the first 50 cytoreductive surgeries and HIPEC by one surgeon for patients 3-21 years of age. The HIPEC was added to chemotherapy and radiotherapy treatment. Demographics, outcome, and complications were recorded. RESULTS: The median follow-up period for the surviving patients was 21.9 months. The most common diagnoses were desmoplastic small round cell tumor (n = 21), rhabdomyosarcoma (n = 7), mesothelioma (n = 4), and other carcinoma (n = 17). Multivariate analysis showed that patients treated with HIPEC and an incomplete cytoreduction had a greater risk for recurrence than those who had a complete cytoreduction (p = 0.0002). The patients with a higher peritoneal cancer index (PCI) (i.e., a large tumor burden) had a median overall survival (OS) time of 19.9 months relative to the patients with a lower PCI score, who had a median OS of 34 months (p = 0.049). The patients without complete cytoreduction had a median OS of 7.1 months compared with 31.4 months for the patients with complete cytoreduction (p = 0.012). No perioperative mortalities occurred. The incidence of major complications was 28 %. CONCLUSION: Cytoreductive surgery and HIPEC with a programmatic approach for patients 3-21 years of age is unique. The best outcome was experienced by patients with desmoplastic small round cell tumor and those with complete cytoreduction. Complete cytoreduction for patients without disease outside the abdominal cavity at the time of surgery affords the best outcome.

Change in postsurgical cavity size within the first 30 days correlates with extent of surrounding edema: consequences for postoperative radiosurgery.

OBJECTIVE: Resection cavity diameter of less than 40 mm is required to be eligible for stereotactic radiosurgery (SRS), after gross total resection of brain metastasis at our institution. Our study evaluates the correlation between vasogenic edema and change in cavity size for 30 days. METHODS: Cavity size was measured on the postoperative and follow-up magnetic resonance imaging. Vasogenic edema was quantified as the largest axial measurement of T2 hyperintensity surrounding the resection cavity (postoperative magnetic resonance imaging). RESULTS: Thirty-nine resection cavities (37 patients) were reviewed. There was a statistically significant (Pearson coefficient = -0.35; P = 0.02) negative correlation between edema and change in cavity size. An arbitrary cutoff value of a 15-mm edema yielded a sensitivity of 96% and a specificity of 65% (P < 0.001) to predict 10% decrease in cavity size. CONCLUSIONS: In patients with cavity size close to the size cutoff for SRS, rescanning closer to the date of SRS should be considered, especially if there is significant edema surrounding the cavity.

The cochlear dose and the age at radiotherapy predict severe hearing loss after passive scattering proton therapy and cisplatin in children with medulloblastoma.

BACKGROUND: Hearing loss (HL) is associated with worse neurocognitive outcomes among patients with medulloblastoma. We aimed to identify risk factors associated with severe HL and to evaluate the generalizability of a published HL calculator among patients treated with passive scattering proton therapy (PSPT) and cisplatin. METHODS: We identified patients aged 3-21 years who were treated at our centers between 2007-2022. Audiograms were graded using the International Society of Pediatric Oncology-Boston scale. Time to grade 3-4 HL was evaluated using Kaplan-Meier and multivariable Cox models to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Seventy-nine patients were treated with PSPT at a median age of 7.5 years (range:3.1-21.1). The mean cochlear dose (Dmc) (±S.D.) was 31.5±8.5 Gy, and the cumulative cisplatin dose was 295±50 mg/m2. Fifty-nine patients (75%) received amifostine. Patients completed a median of 9 audiograms (range:4-22) with a median audiogram follow-up of 49 months (range:6-177). Twenty-seven patients (34%) had grade 3-4 HL. In adjusted Cox models, only higher Dmc (HR=1.12, 95% CI:1.06-1.18) was associated with grade 3-4 HL. The predicted 3-year incidence of grade 3-4 HL was 40.0% (95% CI: 21.3-66.3) and 66.7% (95% CI: 35.4-93.7) for children with Dmc ≥36 Gy and age at radiotherapy ≥7 and <7 years, respectively (p=0.042). It was 8.9% (95% CI: 2.3-31.6) and 15.6% (95% CI: 5.3-41.1) for children with Dmc <36 Gy and age at radiotherapy ≥7 and <7 years, respectively (p=0.78). CONCLUSIONS: Children <7 years at radiotherapy with a Dmc ≥36 Gy are at higher risk for HL.

Comprehensive radiotherapy for pediatric Ewing Sarcoma: Outcomes of a prospective proton study.

BACKGROUND AND PURPOSE: Patients with Ewing Sarcoma (EWS) are treated with multimodality therapy which includes radiation therapy (RT) as an option for local control. We report on the efficacy after proton radiation therapy (PRT) to the primary site for localized and metastatic EWS. MATERIALS AND METHODS: Forty-two children with EWS (33 localized, 9 metastatic) treated between 2007 and 2020 were enrolled on 2 prospective registry protocols for pediatric patients undergoing PRT. PRT was delivered by passive scatter (74 %), pencil-beam scanning (12 %) or mixed technique (14 %). Treated sites included the spine (45 %), pelvis/sacrum (26 %), skull/cranium (14 %), extraosseous (10 %), and chest wall (5 %). Median radiation dose was 54 Gy-RBE (range 39.6-55.8 Gy-RBE). Patients with metastatic disease received consolidative RT to metastatic sites (4 at the time of PRT to the primary site, 5 after completion of chemotherapy). Median follow-up time was 47 months after PRT. RESULTS: The 4-year local control (LC), progression-free survival (PFS), and overall survival (OS) rates were 83 %, 71 %, and 86 %, respectively. All local failures (n = 6) were in-field failures. Tumor size ≥ 8 cm predicted for inferior 4-year LC (69 % vs 95 %, p = 0.04). 4-year PFS and OS rates were not statistically different in patients with localized versus metastatic disease (72 % vs 67 %, p = 0.70; 89 % vs 78 %, p = 0.38, respectively). CONCLUSION: In conclusion, LC for pediatric patients with EWS treated with PRT was comparable to that of historical patients who received photon-RT. Tumor size ≥ 8 cm predicted increased risk of local failure. Patients with metastatic disease, including non-pulmonary only metastases, received radiation therapy to all metastatic sites and had favorable survival outcomes.

Stereotactic radiosurgery for prostate cancer spine metastases: local control and fracture risk using a simultaneous integrated boost approach.

OBJECTIVE: Variation exists in approaches to delivery of spine stereotactic radiosurgery (SSRS). Here, the authors describe outcomes following single-fraction SSRS performed using a simultaneous integrated boost for the treatment of prostate cancer spine metastases. METHODS: Health records of patients with prostate cancer spine metastases treated with single-fraction SSRS at the authors' institution were reviewed. Treatment was uniform, with 16 Gy to the clinical tumor volume and 18 Gy to the gross tumor volume. The primary endpoint was local recurrence, with secondary endpoints including vertebral fracture and overall survival. Univariate and multivariate competing risk regression models made using the Fine and Gray method were used to identify factors predictive of local recurrence, considering death to be a competing event for local recurrence. RESULTS: A total of 87 targets involving 108 vertebrae in 68 patients were included, with a median follow-up of 22.5 months per treated target. The 1-, 2-, and 4-year cumulative incidence rates of local failure for all targets were 4.6%, 8.4%, and 19%, respectively. The presence of epidural disease (subdistribution hazard ratio [sHR] 5.43, p = 0.04) and SSRS as reirradiation (sHR 16.5, p = 0.02) emerged as significant predictors of local failure in a multivariate model. Hormone sensitivity did not predict local control. Vertebral fracture incidence rates leading to symptoms or requiring intervention at 1, 2, and 4 years were 1.1%, 3.7%, and 8.4%, respectively. In an exploratory analysis of patterns of failure, 3 (25%) failures occurred in the epidural space and only 1 (8%) occurred clearly in the clinical tumor volume. There were several lesions for which the precise location of failure with regard to target volumes was unclear. CONCLUSIONS: High rates of local control were observed, particularly for radiotherapy-naïve lesions without epidural disease. Hormone sensitivity was not predictive of local control in this cohort and fracture risk was low. Further research is needed to better predict which patients are at high risk of recurrence and who might benefit from treatment escalation.

Definitive single fraction spine stereotactic radiosurgery for metastatic sarcoma: Simultaneous integrated boost is associated with high tumor control and low vertebral fracture risk.

INTRODUCTION: Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS). MATERIALS AND METHODS: A retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective 95 % confidence intervals (CI). RESULTS: 70 patients with 100 lesions underwent SSRS for SSM. Median follow-up was 19.3 months (IQR 7.7-27.8). Median age was 55 years (IQR42-63). Median GTV and CTVs were 14.5 cm3 (IQR 5-32) and 52.7 cm3 (IQR 29.5-87.5) respectively. Median GTV prescription dose and biologically equivalent dose (BED) [α/ß = 10] was 24 Gy and 81.6 Gy respectively. 85 lesions received 24 Gy to the GTV. 27 % of patients had Bilsky 1b or greater disease. 16 of 100 lesions recurred representing a crude local failure rate of 16 % with a median time to failure of 10.4 months (IQR 5.7-18) in cases which failed locally. 1-year actuarial local control (LC) was 89 %. Median overall survival (OS) was 15.3 months (IQR 7.7-25) from SSRS. Every 1 Gy increase in GTV absolute minimum dose (DMin) across the range (5.8-25 Gy) was associated with a reduced risk of local failure (HR = 0.871 [95 % CI 0.782-0.97], p = 0.009). 9 % of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). CONCLUSION: This study represents one of the most homogenously treated and the largest cohorts of patients with SSM treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates.

Implementation and Efficacy of a Large-Scale Radiation Oncology Case-Based Peer-Review Quality Program across a Multinational Cancer Network.

PURPOSE: With expansion of academic cancer center networks across geographically-dispersed sites, ensuring high-quality delivery of care across all network affiliates is essential. We report on the characteristics and efficacy of a radiation oncology peer-review quality assurance (QA) system implemented across a large-scale multinational cancer network. METHODS AND MATERIALS: Since 2014, weekly case-based peer-review QA meetings have been standard for network radiation oncologists with radiation oncology faculty at a major academic center. This radiotherapy (RT) QA program involves pre-treatment peer-review of cases by disease site, with disease-site subspecialized main campus faculty members. This virtual QA platform involves direct review of the proposed RT plan as well as supporting data, including relevant pathology and imaging studies for each patient. Network RT plans were scored as being concordant or nonconcordant based on national guidelines, institutional recommendations, and/or expert judgment when considering individual patient-specific factors for a given case. Data from January 1, 2014, through December 31, 2019, were aggregated for analysis. RESULTS: Between 2014 and 2019, across 8 network centers, a total of 16,601 RT plans underwent peer-review. The network-based peer-review case volume increased over the study period, from 958 cases in 2014 to 4,487 in 2019. A combined global nonconcordance rate of 4.5% was noted, with the highest nonconcordance rates among head-and-neck cases (11.0%). For centers that joined the network during the study period, we observed a significant decrease in the nonconcordance rate over time (3.1% average annual decrease in nonconcordance, P = 0.01); among centers that joined the network prior to the study period, nonconcordance rates remained stable over time. CONCLUSIONS: Through a standardized QA platform, network-based multinational peer-review of RT plans can be achieved. Improved concordance rates among newly added network affiliates over time are noted, suggesting a positive impact of network membership on the quality of delivered cancer care.

Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.