Technical recommendations for implementation of Volumetric Modulated Arc Therapy and Helical Tomotherapy Total Body Irradiation.

As a component of myeloablative conditioning before allogeneic hematopoietic stem cell transplantation (HSCT), Total Body Irradiation (TBI) is employed in radiotherapy centers all over the world. In recent and coming years, many centers are changing their technical setup from a conventional TBI technique to multi-isocenter conformal arc therapy techniques such as Volumetric Modulated Arc Therapy (VMAT) or Helical Tomotherapy (HT). These techniques allow better homogeneity and control of the target prescription dose, and provide more freedom for individualized organ-at-risk sparing. The technical design of multi-isocenter/multi-plan conformal TBI is complex and should be developed carefully. A group of early adopters with conformal TBI experience using different treatment machines and treatment planning systems came together to develop technical recommendations and share experiences, in order to assist departments wishing to implement conformal TBI, and to provide ideas for standardization of practices.

Automated contouring, treatment planning, and quality assurance for VMAT craniospinal irradiation (VMAT-CSI).

Purpose: Create a comprehensive automated solution for pediatric and adult VMAT-CSI including contouring, planning, and plan check to reduce planning time and improve plan quality. Methods: Seventy-seven previously treated CSI patients (age, 2-67 years) were used for creation of an auto-contouring model to segment 25 organs at risk (OARs). The auto-contoured OARs were evaluated using the Dice Similarity Coefficient (DSC), 95% Hausdorff Distance (HD95), and a qualitative ranking by one physician and one physicist (scale: 1-acceptable, 2-minor edits, 3-major edits). The auto-planning script was developed using the Varian Eclipse Scripting API and tested with 20 patients previously treated with either low-dose VMAT-CSI (12 Gy) or high-dose VMAT-CSI (36 Gy + 18 Gy boost). Clinically relevant metrics, planning time, and blinded physician review were used to evaluate significance of differences between the auto and manual plans. Finally, the plan preparation for treatment and plan check processes were automated to improve efficiency and safety of VMAT-CSI. Results: The auto-contours achieved an average DSC of 0.71 ± 0.15, HD95 of 4.81 ± 4.68, and reviewers' ranking of 1.22 ± 0.39, indicating close to "acceptable-as-is" contours. Compared to the manual CSI plans, the auto-plans for both dose regimens achieved statistically significant reductions in body V50% and Dmean for parotids, submandibular, and thyroid glands. The variance in the dosimetric parameters decreased for the auto-plans as compared to the manual plans indicating better plan consistency. From the blinded review, the auto-plans were marked as equivalent or superior to the manual-plans 88.3% of the time. The required time for the auto-contouring and planning was consistently between 1-2 hours compared to an estimated 5-6 hours for manual contouring and planning. Conclusions: Reductions in contouring and planning time without sacrificing plan quality were obtained using the developed auto-planning process. The auto-planning scripts and documentation will be made freely available to other institutions and clinics.

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.

Automating the Treatment Planning Process for Volumetric Modulated Arc Therapy Craniospinal Irradiation.

PURPOSE: The purpose of this work is to develop a method to automate the treatment planning process of craniospinal irradiation (CSI) using volumetric modulated arc therapy. METHODS AND MATERIALS: Two scripts were developed using the Eclipse Scripting Application Programming Interface to perform auto-plan preparation and optimization. Ten patients (age, 5-44 years) previously treated at our institution with low dose volumetric modulated arc therapy CSI (prescription of 12 Gy) before total body irradiation were selected to evaluate the efficacy of the proposed auto-planning process. Paired t tests compared the dosimetric indices of the auto-plans to the manually generated clinical plans. All plans were normalized to 95% of planning target volume (PTV) coverage with the prescription dose. Two physicians and one physicist were asked to evaluate the manual plans and auto-plans of each patient in a blinded retrospective review and to indicate clinical acceptability and which plans were preferred for treatment. RESULTS: Compared with the manual CSI plans, the auto plans obtained significant reductions in Dmean to the parotids, submandibular glands, larynx, thyroid, and significant reduction in the plan PTV Dmax and D0.03 cc. The standard deviation range of the dosimetric parameters was greatly reduced for auto plans (range, 0.1-1.3 Gy) relative to manual plans (range, 0.4-5.9 Gy) indicating better plan consistency. Among the 10 patients, the auto-plans were preferred over the manual plans 90% of the time by the reviewing experts. The required time for auto-planning was approximately 1 hour compared with estimated 4 or more hours for manual planning. CONCLUSIONS: Reductions in planning time without sacrifices in plan quality were obtained using the auto-planning process compared with manual planning. Variation in plan quality was also reduced. The auto-planning scripts will be made freely available to other institutions and clinics.

Patterns of Local Recurrence and Risk of Skin Recurrence in Soft Tissue Sarcomas After Surgical Resection.

PURPOSE: Although there is a theoretical risk of skin seeding during surgical resection of soft tissue sarcomas (STSs), current consensus guidelines recommend against routine use of bolus during radiation therapy (RT). However, the risk of skin recurrence has not been systematically assessed. We aimed to assess the patterns of local recurrence (LR) in patients with STS treated with surgery with or without RT. METHODS AND MATERIALS: We performed a retrospective analysis of adults with STSs evaluated at our institution between 2007 and 2021. For patients who developed LR, the depth was evaluated. Progression-free survival and overall survival were analyzed from time of first LR using the Kaplan-Meier method. Cumulative incidence of distant metastasis was calculated with competing risk analysis from date of LR. RESULTS: Of the 206 patients evaluated, 20 had LR (9.7%). Among patients with LR, 5 patients (25.0%) were treated with surgery alone and 15 patients (75.0%) with surgery and RT. In patients treated with RT, 46.7% had preoperative RT, 53.3% had postoperative RT, and bolus was used in 46.7%. Surgical margins were close (<1 mm) in 4 patients (20.0%) and positive in 10 patients (50.0%). LR occurred in the deep subfascial tissue in 9 patients (45%), subcutaneous tissue in 10 patients (50.0%), and skin in 1 patient (5.0%). The patient with a skin recurrence was treated with surgery alone, and the tumor involved the skin at presentation. In patients treated with RT, LR occurred within the RT field in 13 patients (86.7%). At 1 year after LR, progression-free survival was 70.3%, overall survival was 81.7%, and cumulative incidence of distant metastasis was 5.9%. CONCLUSIONS: Skin recurrences were rare after surgical resection of STSs and only occurred in a tumor that involved the skin at initial presentation. These findings support current recommendations against routine use of bolus in STSs not involving the skin at presentation.

Prognosis of children and young adults with newly diagnosed rhabdomyosarcoma metastatic to bone marrow treated on Children's Oncology Group studies.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Metastatic disease occurs in 16% of all RMS cases and has a poor prognosis. There are limited studies examining the outcomes specific to patients with RMS metastatic to bone marrow despite an incidence of 6% at diagnosis. Our study aims to document the outcomes, prognostic factors, and clinical courses of children presenting with RMS metastatic to bone marrow treated on Children's Oncology Group (COG) cooperative trials. METHODS: We performed a retrospective analysis of the patients diagnosed with RMS metastatic to bone marrow between 1997 and 2013 enrolled on one of four COG RMS clinical trials of D9802, D9803, ARST0431, and ARST08P1. RESULTS: We identified 179 cases with RMS metastatic to bone marrow. Patients had a median age of 14.8 years, 58% were male, predominantly alveolar histology (76%), extremity was the most common primary site (32%), and 87% had metastatic disease to additional sites; 83% (n = 149) received radiation as a treatment modality. The 3- and 5-year event-free survival was 9.4% and 8.2%, respectively. The 3- and 5-year overall survival was 26.1% and 12.6%, respectively. Age ≥10 years, alveolar histology, FOXO1 fusion presence, unfavorable primary location, higher Oberlin score, and lack of radiation were identified as poor prognostic/predictive characteristics. CONCLUSIONS: This study represents the largest analysis of RMS metastatic to bone marrow, defining the poor prognostic outcome for these patients. These patients may be eligible for therapy deintensification or early pursuit of novel treatments/approaches that are desperately needed.

Improved organ sparing using auto-planned Stanford volumetric modulated arc therapy for total body irradiation technique.

PURPOSE/OBJECTIVES: To evaluate dosimetric differences between auto-planned volumetric modulated arc therapy (VMAT) total body irradiation (TBI) technique and two-dimensional radiotherapy using anterior-posterial/posterio-anterial beams (2D AP/PA) TBI technique. METHODS: Ten pediatric patients treated with VMAT-TBI on Varian c-arm linac were included in this study. VMAT-TBI plans were generated using our in-house developed and publicly shared auto-planning scripts. For each VMAT-TBI plan, a 2D AP/PA plan was created replicating the institution's clinical setup with the patient positioned at extended source to skin distance (SSD) with a compensator to account for differences in patient thickness, 50% transmission daily lung blocks, and electron chest wall boosts prescribed to 50% of the photon prescription. Clinically relevant metrics were analyzed and compared between the VMAT and 2D plans. RESULTS: All VMAT-TBI plans achieved planned target volume (PTV) D90% ≥ 100% of prescription. VMAT-TBI PTV D90% significantly increased (7.1% ± 2.9%, p < .001) compared to the 2D technique, whereas no differences were observed in global Dmax (p < .2) and PTV V110% (p < .4). Compared to the 2D plans, significant decreases in the Dmean to the lungs (-25.6% ± 11.5%, p < .001) and lungs-1 cm (-34.1% ± 10.1%, p < .001) were observed with the VMAT plans. The VMAT technique also enabled decrease of dose to other organs: kidneys Dmean (-32.5% ± 5.0%, p < .001) and lenses Dmax (-5.3% ± 8.1%, p = .03); and in addition, for 2 Gy prescription: testes/ovaries Dmean (-41.5% ± 11.5%, p < .001), brain Dmean (-22.6% ± 5.4%, p = .002), and thyroid Dmean (-18.2% ± 16.0%, p = .03). CONCLUSIONS: Superior lung sparing with improved target coverage and similar global Dmax were observed with the VMAT plans as compared to 2D plans. In addition, VMAT-TBI plans provided greater dose reductions in gonads, kidneys, brain, thyroid, and lenses.

Central Endocrine Complications Among Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

PURPOSE: Children who receive cranial radiation therapy (RT) as a component of treatment for malignancy are often at risk of long-term central endocrine toxicity secondary to radiation to the hypothalamic-pituitary axis (HPA). A comprehensive analysis was performed of central endocrine late effects in survivors of childhood cancer treated with RT as part of the Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium. METHODS AND MATERIALS: A systematic review of the risk of RT-related central endocrine effects was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 4629 publications were identified, of which 16 met criteria for inclusion in dose modeling analysis, with a total of 570 patients in 19 cohorts. Eighteen cohorts reported outcomes for growth hormone deficiency (GHD), 7 reported outcomes for central hypothyroidism (HT), and 6 reported outcomes for adrenocorticotropic hormone (ACTH) deficiency. RESULTS: Normal tissue complication probability modeling for GHD (18 cohorts, 545 patients) yielded D50 = 24.9 Gy (95% CI, 20.9-28.0) and γ50 = 0.5 (95% CI, 0.27-0.78). The normal tissue complication probability model fit for whole brain irradiation in children with a median age of >5 years indicated a 20% risk of GHD for patients who receive a mean dose of 21 Gy in 2-Gy fractions to the HPA. For HT, among 7 cohorts (250 patients), D50 = 39 Gy (95% CI, 34.1-53.2) and γ50 = 0.81 (95% CI, 0.46-1.35), with a 20% risk of HT in children who receive a mean dose of 22 Gy in 2-Gy fractions to the HPA. For ACTH deficiency (6 cohorts, 230 patients), D50 = 61 Gy (95% CI, 44.7-119.4) and γ50 = 0.76 (95% CI, 0.5-1.19); there is a 20% risk of ACTH deficiency in children who receive a mean dose of 34 Gy in 2-Gy fractions to the HPA. CONCLUSIONS: RT dose to the HPA increases the risk of central endocrine toxicity, including GHD, HT, and ACTH deficiency. In some clinical situations, these toxicities may be difficult to avoid, and counseling of patients and families with respect to anticipated outcomes is important.

Feasibility of the Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) System for Anesthesia Avoidance in Pediatric Patients: A Multicenter Trial.

PURPOSE: The Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) system was the first published radiation therapy (RT)-compatible system to reduce the need for pediatric anesthesia through video-based distraction. We evaluated the feasibility of AVATAR implementation and effects on anesthesia use, quality of life, and anxiety in a multicenter pediatric trial. METHODS AND MATERIALS: Pediatric patients 3 to 10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled. Children able to undergo at least 1 fraction of RT using AVATAR without anesthesia were considered successful (S). Patients requiring anesthesia for their entire treatment course were nonsuccessful (NS). The PedsQL3.0 Cancer Module (PedsQL) survey assessed quality of life and was administered to the patient and guardian at RT simulation, midway through RT, and at final treatment. The modified Yale Preoperative Anxiety Scale (mYPAS) assessed anxiety and was performed at the same 3 time points. Success was evaluated using the χ2 test. PedsQL and mYPAS scores were assessed using mixed effects models with time points evaluated as fixed effects and a random intercept on the subject. RESULTS: Eighty-one children were included; median age was 7 years. AVATAR was successful at all 10 institutions and with photon and proton RT. There were 63 (78%) S patients; anesthesia was avoided for a median of 20 fractions per patient. Success differed by age (P = .04) and private versus public insurance (P < .001). Both patient (P = .008) and parent (P = .006) PedsQL scores significantly improved over the course of RT for patients aged 5 to 7. Anxiety in the treatment room decreased for both S and NS patients over RT course (P < .001), by age (P < .001), and by S versus NS patients (P < .001). CONCLUSIONS: In this 10-center prospective trial, anesthesia avoidance with AVATAR was 78% in children aged 3 to 10 years, higher than among age-matched historical controls (49%; P < .001). AVATAR implementation is feasible across multiple institutions and should be further studied and made available to patients who may benefit from video-based distraction.

Rhabdomyosarcoma with isolated lung metastases: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

BACKGROUND: To determine outcomes of children with rhabdomyosarcoma (RMS) with isolated lung metastases. METHODS: Data were analyzed for 428 patients with metastatic RMS treated on COG protocols. Categorical variables were compared using Chi-square or Fisher's exact tests. Event-free survival (EFS) and overall survival (OS) were estimated using Kaplan-Meier method and compared using the log-rank test. RESULTS: Compared with patients with other metastatic sites (n = 373), patients with lung-only metastases (n = 55) were more likely to be <10 years of age, have embryonal histology (embryonal rhabdomyosarcoma), have N0 disease, and less likely to have primary extremity tumors. Lung-only patients had significantly better survival outcomes than patients with all other sites of metastatic disease (p < .0001) with 5-year EFS of 48.1 versus 18.8% and 5-year OS of 64.1 versus 26.9%. Patients with lung-only metastases, and those with a single extrapulmonary site of metastasis, had better survival compared with patients with two or more sites of metastatic disease (p < .0001). In patients with ERMS and lung-only metastases, there was no significant difference in survival between patients ≥10 years and 1-9 years (5-year EFS: 58.3 vs. 68.2%, 5-year OS: 66.7 vs. 67.7%). CONCLUSIONS: With aggressive treatment, patients with ERMS and lung-only metastatic disease have superior EFS and OS compared with patients with other sites of metastatic disease, even when older than 10 years of age. Consideration should be given to including patients ≥10 years with ERMS and lung-only metastases in the same group as those <10 years in future risk stratification algorithms.

Investigating and modeling positron emission tomography factors associated with large cell transformation from low-grade lymphomas.

Low-grade lymphomas have a 1%-3% annual risk of transformation to a high-grade histology, and prognostic factors remain undefined. We set to investigate the role of positron emission tomography (PET) metrics in identification of transformation in a retrospective case-control series of patients matched by histology and follow-up time. We measured PET parameters including maximum standard uptake value (SUV-max) and total lesion glycolysis (TLG), and developed a PET feature and lactate dehydrogenase (LDH)-based model to identify transformation status within discovery and validation cohorts. For our discovery cohort, we identified 53 patients with transformation and 53 controls with a similar distribution of follicular lymphoma (FL). Time to transformation and control follow-up time was similar. We observed a significant incremental increase in SUV-max and TLG between control, pretransformation and post-transformation groups (P < 0.05). By multivariable analysis, we identified a significant interaction between SUV-max and TLG such that SUV-max had highest significance for low volume cases (P = 0.04). We developed a scoring model incorporating SUV-max, TLG, and serum LDH with improved identification of transformation (area under the curve [AUC] = 0.91). Our model performed similarly for our validation cohort of 23 patients (AUC = 0.90). With external and prospective validation, our scoring model may provide a specific and noninvasive tool for risk stratification for patients with low-grade lymphoma.

Radiation Therapy for Primary Cutaneous Gamma Delta Lymphoma Prior to Stem Cell Transplantation.

We present a patient with widespread PCGD-TCL of the bilateral arms and legs, who underwent radiotherapy with 34 Gy in 17 fractions using circumferential VMAT and 3-D printed bolus to the four extremities prior to planned stem cell transplant, who was then found to have progression in the liver, lung, and skin, followed by drastic regression of all in and out-of-field lesions on imaging 1.5 months later. The cause of regression may be related to a radiation-induced abscopal effect from the immunomodulatory effects of radiation, or related to immune reactivation in the setting of cessation of systemic immunosuppressive agents.

Long-term Outcomes of Diffuse or Recurrent Tenosynovial Giant Cell Tumor Treated with Postoperative External Beam Radiation Therapy.

PURPOSE: Tenosynovial giant cell tumor (TGCT) is a rare proliferative disorder of synovial membrane that previously was known as pigmented villonodular synovitis. Primary treatment involves surgical resection; however, complete removal of all disease involvement is difficult to achieve. Radiation may be useful to reduce the risk of recurrence. We report and update our institutional experience treating diffuse and recurrent TGCT with postsurgical external beam radiation therapy. METHODS AND MATERIALS: We performed a retrospective chart review of 30 patients with TGCT from 2003 to 2019 treated with radiation therapy. Each patient was evaluated for demographics, radiation treatment parameters, surgical management, complications, and outcome. RESULTS: With mean follow-up of 82 months (range, 3-211), 24 patients (80%) who underwent surgery followed by radiation therapy did not experience any further relapse, and all 30 patients achieved local control (100%) with additional salvage therapy after radiation therapy. The most common site of disease was the knee (n = 22, 73%), followed by the ankle (n = 5, 16%) and the hand (n = 3, 10%). Seven patients (24%) presented at time of initial diagnosis and 23 (76%) presented with recurrent disease after surgical resection, with an average of 2.6 surgical procedures before radiation therapy. After resection, 18 of 30 patients (67%) demonstrated residual TGCT by imaging. The median radiation therapy dose delivered was 36 Gy (range, 34-36 Gy) in 1.8 to 2.5 Gy/fractions for 4 weeks. In the assessment of posttreatment joint function, 26 sites (86%) exhibited excellent or good function, 2 (7%) fair, and 2 poor (7%) as determined by our scoring system. There were no cases of radiation-associated malignancy. CONCLUSIONS: Among patients with diffuse or recurrent TGCT, postsurgical external beam radiation therapy provided excellent local control and good functional status, with minimal treatment-related complications. Postsurgical radiation therapy is a well-tolerated noninvasive treatment that should be considered after maximal cytoreductive resection to prevent disease progression and recurrence.

Effect of Testicular Boost in Children With Leukemia Receiving Total Body Irradiation and Stem Cell Transplant: A Single-Institution Experience.

Purpose: Children with leukemia who receive fractionated total body irradiation (fTBI) with 12 to 13.2 Gy as part of conditioning for hematopoietic stem cell transplant are frequently treated with an additional 4 Gy testicular boost to reduce the risk of testicular relapse. While institutional practices vary, limited data exists regarding whether the 4-Gy testicular boost reduces the risk of relapse and whether it causes toxicity beyond that imparted by TBI. This study compared the survival and endocrine outcomes among the patients who were treated with and without a testicular boost as part of fTBI from 1990 to 2019 at our center. Methods and Materials: We retrospectively reviewed charts of male children with leukemia treated with fTBI as part of a conditioning regimen for stem cell transplant from 1990 to 2019. Reported outcomes included progression-free survival, testicular relapse rate, and overall survival. Gonadal dysfunction and fertility were assessed by comparing the rate of abnormally low testosterone or high luteinizing hormone or follicular stimulating hormone, number of offspring, fertility service use, and abnormal sperm count in the subsequent follow-up period between the testicular boost and nonboost subset. Results: Ninety-three male patients (63 acute lymphoblastic leukemia, 30 acute myeloid leukemia) with a median age of 9 years (range, 1-22) and follow-up of 3.3 years were included. In addition to 12- to 13.2-Gy fTBI, 51 male patients (54%) received a testicular boost to 4 Gy. There was 1 testicular relapse in the boost subset and none in the nonboost subset. Five-year progression-free survival for the boost and nonboost subset was 74% and 66%, respectively (P = .31). On multivariable analysis, boost was not associated with improved relapse-free survival or overall survival. More patients in the boost subset (35 of 51, 69%) had abnormal serum gonadal blood work compared with the nonboost subset (18 of 42, 43%) (P = .03). Conclusions: Omission of testicular boost may be associated with comparable oncologic but improved gonadal endocrine outcomes and should be further studied.

Time to resolution of iodine-123 metaiodobenzylguanidine (123 I-MIBG) avidity and local control outcomes for high-risk neuroblastoma following radiation therapy.

INTRODUCTION: 123 I-MIBG scan is used in neuroblastoma (NB) to monitor treatment response. Time to resolution of 123 I-MIBG avidity after radiation therapy (RT) is unknown. We sought to determine time to resolution of 123 I-MIBG avidity after RT and local failure (LF) rate. METHODS: We performed a retrospective review of children with high-risk NB who underwent 123 I-MIBG scans pre- and post-RT from 2003 to 2019. Time from RT to resolution of 123 I-MIBG activity was analysed. LF and cumulative incidence of local progression (CILP) after RT stratified by site, presence of residual disease and use of boost RT were determined. RESULTS: Forty-two patients with median age 3.9 years (1.9-4.7 years) were included, with median follow-up time 3.9 years (1.4-6.9). Eighty-six lesions were treated with RT to median dose of 21.6 Gy. Eighteen of 86 lesions were evaluable for time to resolution of MIBG avidity after RT, with median resolution time of 78 days (36-208). No LF occurred among 26 patients who received RT to primary sites after GTR, versus 4/12 (25%) patients treated with residual primary disease. 2-year CILP was 19% (12% primary disease 25% metastatic disease (P = 0.18)). 2-year CILP for non-residual primary, residual primary, non-residual metastatic and residual metastatic lesions was 0%, 42%, 11% and 30% respectively (P = 0.01) and for boosted and non-boosted residual lesions was 29% and 35% (P = 0.44). CONCLUSION: Median time to MIBG resolution after RT was 78 days. Primary lesions without residual disease had excellent local control. LF rate was higher after RT for residual disease, with no benefit for boost RT.

Stereotactic radiosurgery for recurrent pediatric brain tumors: clinical outcomes and toxicity.

OBJECTIVE: Recurrence of brain tumors in children after the initial course of treatment remains a problem. This study evaluated the efficacy and safety of reirradiation using stereotactic radiosurgery (SRS) in patients with recurrent pediatric primary brain tumors. METHODS: This IRB-approved retrospective review included pediatric patients with recurrent primary brain tumors treated at Stanford University from 2000 to 2019 using frameless SRS. Time to local failure (LF) and distant intracranial failure (DIF) were measured from the date of SRS and analyzed using competing risk analysis. Overall survival (OS) and progression-free survival (PFS) were analyzed with the Kaplan-Meier method. RESULTS: In total, 37 patients aged 2-24 years (median age 11 years at recurrence) were treated for 48 intracranial tumors. Ependymoma (38%) and medulloblastoma (22%) were the most common tumor types. The median (range) single fraction equivalent dose of SRS was 16.4 (12-24) Gy. The median (range) follow-up time was 22.9 (1.5-190) months. The median OS of all patients was 36.8 months. Eight of 40 (20%) lesions with follow-up imaging locally recurred. The 2-year cumulative incidence of LF after reirradiation with SRS was 12.8% (95% CI 4.6%-25.4%). The 2-year cumulative incidence of DIF was 25.3% (95% CI 12.9%-39.8%). The median PFS was 18 months (95% CI 8.9-44). Five (10.4%) patients developed toxicities potentially attributed to SRS, including cognitive effects and necrosis. CONCLUSIONS: Reirradiation using SRS for recurrent pediatric brain tumors appears safe with good local control. Innovations that improve overall disease control should continue because survival outcomes after relapse remain poor.

Local Control Outcomes Using Stereotactic Body Radiation Therapy or Surgical Resection for Metastatic Sarcoma.

PURPOSE: Traditional management of metastatic sarcoma primarily relies on systemic therapy, with surgery often used for tumor control. We analyzed the rates of recurrence, overall survival, and treatment complications in patients undergoing either surgical resection or stereotactic body radiation therapy (SBRT) for metastatic sarcoma of the bone and/or soft tissue. METHODS AND MATERIALS: The records of patients with metastatic sarcoma between 2009 and 2020 were reviewed. Local recurrence (LR) was defined as tumor growth or recurrence at the tumor site. Cumulative LR incidence was analyzed accounting for the competing risk of death, and groups were compared using the Gray test. Overall survival (OS) was assessed using the Kaplan-Meier method and log-rank test. Hazard ratios were determined using the Cox proportional hazards model. RESULTS: A total of 525 metastatic lesions in 217 patients were analyzed. The mean age of patients was 57 years (range, 4-88 years). The lung was the predominant site treated (50%), followed by intra-abdominal (13%) and soft tissue (11%). Two-year cumulative incidences of LR for surgery and SBRT were 14.8% (95% confidence interval [CI], 11.6%-18.5%) and 1.7% (95% CI, 0.1%-8.2%), respectively (P = .003). Local recurrence occurred in 72 (16.5%) of 437 tumors treated with surgery and 2 (2.3%) of 88 tumors treated with SBRT. The adjusted hazard ratio for LR of lesions treated surgically was 11.5 (P = .026) when controlling for tumor size and tumor site. Median OS was 29.8 months (95% CI, 25.6-40.9 months). There were 47 surgical complications among a total of 275 procedures (18%). Of 58 radiation treatment courses, radiation-related toxic effects were reported during the treatment of 7 lesions (12%), and none were higher than grade 2. CONCLUSIONS: We observed excellent local control among patients selected for treatment with SBRT for metastatic sarcoma, with no evidence of an increase in LR after SBRT compared with surgical management. Further investigation is necessary to better define the most appropriate local control strategies for metastatic sarcoma.

Volumetric modulated arc therapy total body irradiation in pediatric and adolescent/young adult patients undergoing stem cell transplantation: Early outcomes and toxicities.

INTRODUCTION: Total body irradiation (TBI) is an important component of many conditioning regimens for hematopoietic stem cell transplantation (HSCT), most commonly used in pediatric and adolescent/young adult (AYA) patients. We aimed to evaluate outcomes and toxicities among pediatric and AYA patients treated with TBI utilizing volumetric modulated arc therapy total body irradiation (VMAT-TBI). METHODS: We reviewed pediatric and AYA patients treated with VMAT-TBI at our institution from 2019 to 2021. Data on patient and disease characteristics, treatment details, outcomes and toxicities were collected. Overall survival (OS) and relapse-free survival (RFS) were analyzed using the Kaplan-Meier method. RESULTS: Among 38 patients, 16 (42.1%) were treated with myeloablative regimens and 22 (57.9%) with nonmyeloablative regimens. Median age was 7.2 years (range: 1-27) and median follow-up was 8.7 months (range: 1-21). Lungs Dmean was 7.3 ± 0.3 Gy for myeloablative regimens (range: 6.8-7.8). Kidneys were spared to average mean dose of 71.4 ± 4.8% of prescription dose. Gonadal sparing was achieved for patients treated for nonmalignant diseases to Dmean of 0.7 ± 0.1 Gy. No patient experienced primary graft failure; one (2.6%) experienced secondary graft failure. The most common grade 1-2 acute toxicities were nausea (68.4%) and fatigue (55.3%). Mucositis was the most common grade 3-4 acute toxicity, affecting 39.5% of patients. There were no cases of pneumonitis or nephrotoxicity attributable to TBI. CONCLUSION: VMAT-TBI offers increased ability to spare organs at risk in pediatric and AYA patients undergoing HSCT, with a favorable acute/subacute toxicity profile and excellent disease control.

Detection of Recurrence After Thoracic Stereotactic Ablative Radiotherapy Using FDG-PET-CT.

INTRODUCTION/BACKGROUND: Differentiating local recurrence (LR) from post-treatment changes following stereotactic ablative radiotherapy (SABR) for thoracic tumors is challenging. We sought to evaluate the performance of FDG-PET-CT in distinguishing recurrence from post-radiation changes in patients with stage I-II non-small cell lung cancer (NSCLC) treated with SABR. MATERIALS AND METHODS: We performed a retrospective review of patients with stage I-II NSCLC treated with SABR and subsequently followed with surveillance FDG-PET-CT scans from 2004 to 2014. The radiology reports were coded as 0 or 1 if minimally or substantially concerning for LR, respectively, and correlated with outcome. Prognostic factors for false-positive FDG-PET-CT were assessed using logistic regression models. RESULTS: We identified 145 patients meeting inclusion criteria for the retrospective analysis. Amongst the 39 (26.9%) patients with FDG-PET-CT scans concerning for LR 3 to 24 months after treatment, 14 were confirmed to have LR. Thus, the positive predictive value (PPV) of FDG-PET-CT in identifying LR was 36% (14/39). Factors associated with a false-positive scan included concerning FDG-PET-CT at the earliest post-treatment time point (3 months) (odds ratio 0.67, P= .04) and older age (odds ratio 2.3, P= .02). CONCLUSION: Our analysis indicates that the PPV of a concerning FDG-PET-CT after SABR for early-stage NSCLC is relatively low, especially at early post-treatment timepoints, but accuracy is improving over time with institutional experience.