Practice Patterns of Stereotactic Radiotherapy in Pediatrics: Results From an International Pediatric Research Consortium.

PURPOSE/OBJECTIVES: There is little consensus regarding the application of stereotactic radiotherapy (SRT) in pediatrics. We evaluated patterns of pediatric SRT practice through an international research consortium. MATERIALS AND METHODS: Eight international institutions with pediatric expertise completed a 124-item survey evaluating patterns of SRT use for patients 21 years old and younger. Frequencies of SRT use and median margins applied with and without SRT were evaluated. RESULTS: Across institutions, 75% reported utilizing SRT in pediatrics. SRT was used in 22% of brain, 18% of spine, 16% of other bone, 16% of head and neck, and <1% of abdomen/pelvis, lung, and liver cases across sites. Of the hypofractionated SRT cases, 42% were delivered with definitive intent. Median gross tumor volume to planning target volume margins for SRT versus non-SRT plans were 0.2 versus 1.4 cm for brain, 0.3 versus 1.5 cm for spine/other bone, 0.3 versus 2.0 cm for abdomen/pelvis, 0.7 versus 1.5 cm for head and neck, 0.5 versus 1.7 cm for lung, and 0.5 versus 2.0 cm for liver sites. CONCLUSIONS: SRT is commonly utilized in pediatrics across a range of treatment sites. Margins used for SRT were substantially smaller than for non-SRT planning, highlighting the utility of this approach in reducing treatment volumes.

Practice patterns of palliative radiation therapy in pediatric oncology patients in an international pediatric research consortium.

BACKGROUND/OBJECTIVES: The practice of palliative radiation therapy (RT) is based on extrapolation from adult literature. We evaluated patterns of pediatric palliative RT to describe regimens used to identify opportunity for future pediatric-specific clinical trials. DESIGN/METHODS: Six international institutions with pediatric expertise completed a 122-item survey evaluating patterns of palliative RT for patients ≤21 years old from 2010 to 2015. Two institutions use proton RT. Palliative RT was defined as treatment with the goal of symptom control or prevention of immediate life-threatening progression. RESULTS: Of 3,225 pediatric patients, 365 (11%) were treated with palliative intent to a total of 427 disease sites. Anesthesia was required in 10% of patients. Treatment was delivered to metastatic disease in 54% of patients. Histologies included neuroblastoma (30%), osteosarcoma (18%), leukemia/lymphoma (12%), rhabdomyosarcoma (12%), medulloblastoma/ependymoma (12%), Ewing sarcoma (8%), and other (8%). Indications included pain (43%), intracranial symptoms (23%), respiratory compromise (14%), cord compression (8%), and abdominal distention (6%). Sites included nonspine bone (35%), brain (16% primary tumors, 6% metastases), abdomen/pelvis (15%), spine (12%), head/neck (9%), and lung/mediastinum (5%). Re-irradiation comprised 16% of cases. Techniques employed three-dimensional conformal RT (41%), intensity-modulated RT (23%), conventional RT (26%), stereotactic body RT (6%), protons (1%), electrons (1%), and other (2%). The most common physician-reported barrier to consideration of palliative RT was the concern about treatment toxicity (83%). CONCLUSION: There is significant diversity of practice in pediatric palliative RT. Combined with ongoing research characterizing treatment response and toxicity, these data will inform the design of forthcoming clinical trials to establish effective regimens and minimize treatment toxicity for this patient population.

Optimized Conformal Total Body Irradiation methods with Helical TomoTherapy and Elekta VMAT: Implementation, Imaging, Planning and Dose Delivery for Pediatric Patients.

Optimized conformal total body irradiation (OC-TBI) is a highly conformal image guided method for irradiating the whole human body while sparing the selected organs at risk (OARs) (lungs, kidneys, lens). This study investigated the safety and feasibility of pediatric OC-TBI with the helical TomoTherapy (TomoTherapy) and volumetric modulated arc (VMAT) modalities and their implementation in routine clinical practice. This is the first study comparing the TomoTherapy and VMAT modalities in terms of treatment planning, dose delivery accuracy, and toxicity for OC-TBI in a single-center setting. The OC-TBI method with standardized dosimetric criteria was developed and implemented with TomoTherapy. The same OC-TBI approach was applied for VMAT. Standardized treatment steps, namely, positioning and immobilization, contouring, treatment planning strategy, plan evaluation, quality assurance, visualization and treatment delivery procedure were implemented for 157 patients treated with TomoTherapy and 52 patients treated with VMAT. Both modalities showed acceptable quality of the planned target volume dose coverage with simultaneous OARs sparing. The homogeneity of target irradiation was superior for TomoTherapy. Overall assessment of the OC-TBI dose delivery was performed for 30 patients treated with VMAT and 30 patients treated with TomoTherapy. The planned and delivered (sum of doses for all fractions) doses were compared for the two modalities in groups of patients with different heights. The near maximum dose values of the lungs and kidneys showed the most significant variation between the planned and delivered doses for both modalities. Differences in the patient size did not result in statistically significant differences for most of the investigated parameters in either the TomoTherapy or VMAT modality. TomoTherapy-based OC-TBI showed lower variations between planned and delivered doses, was less time-consuming and was easier to implement in routine practice than VMAT. We did not observe significant differences in acute and subacute toxicity between TomoTherapy and VMAT groups. The late toxicity from kidneys and lungs was not found during the 2.3 years follow up period. The study demonstrates that both modalities are feasible, safe and show acceptable toxicity. The standardized approaches allowed us to implement pediatric OC-TBI in routine clinical practice.

Optimized Conformal Total Body Irradiation Among Recipients of TCRαß/CD19-Depleted Grafts in Pediatric Patients With Hematologic Malignancies: Single-Center Experience.

Total body irradiation (TBI) in combination with chemotherapy is widely used as a conditioning regimen in pediatric and adult hematopoietic stem cell transplantation (HSCT). The combination of TBI with chemotherapy has demonstrated superior survival outcomes in patients with acute lymphoblastic and myeloid leukemia when compared with conditioning regimens based only on chemotherapy. The clinical application of intensity-modulated radiation therapy (IMRT)-based methods (volumetric modulated arc therapy (VMAT) and TomoTherapy) seems to be promising and has been actively used worldwide. The optimized conformal total body irradiation (OC-TBI) method described in this study provides selected dose reduction for organs at risk with respect to the most significant toxicity (lungs, kidneys, lenses). This study included 220 pediatric patients who received OC-TBI with subsequent chemotherapy and allogenic HSCT with TCRαß/CD19 depletion. A group of 151 patients received OC-TBI using TomoTherapy, and 40 patients received OC-TBI using the Elekta Synergy™ linac with an Agility-MLC (Elekta, Crawley, UK) using volumetric modulated arc therapy (VMAT). Twenty-nine patients received OC-TBI with supplemental simultaneous boost to bone marrow-(SIB to BM) up to 15 Gy: 28 patients (pts)-TomoTherapy; one patient-VMAT. The follow-up duration ranged from 0.3 to 6.4 years (median follow-up, 2.8 years). Overall survival (OS) for all the patients was 63% (95% CI: 56-70), and event-free survival (EFS) was 58% (95% CI: 51-65). The cumulative incidence of transplant-related mortality (TRM) was 10.7% (95% CI: 2.2-16) for all patients. The incidence of early TRM (<100 days) was 5.0% (95% CI: 1.5-8.9), and that of late TRM (>100 days) was 5.7 (95% CI: 1.7-10.2). The main causes of death for all the patients were relapse and infection. The concept of OC-TBI using IMRT VMAT and helical treatment delivery on a TomoTherapy treatment unit provides maximum control of the dose distribution in extended targets with simultaneous dose reduction for organs at risk. This method demonstrated a low incidence of severe side effects after radiation therapy and predictable treatment effectiveness. Our initial experience demonstrates that OC-TBI appears to be a promising technique for the treatment of pediatric patients.

Low-Dose Image-Guided Pediatric CNS Radiation Therapy: Final Analysis From a Prospective Low-Dose Cone-Beam CT Protocol From a Multinational Pediatrics Consortium.

BACKGROUND: Lower-dose cone-beam computed tomography protocols for image-guided radiotherapy may permit target localization while minimizing radiation exposure. We prospectively evaluated a lower-dose cone-beam protocol for central nervous system image-guided radiotherapy across a multinational pediatrics consortium. METHODS: Seven institutions prospectively employed a lower-dose cone-beam computed tomography central nervous system protocol (weighted average dose 0.7 mGy) for patients ≤21 years. Treatment table shifts between setup with surface lasers versus cone-beam computed tomography were used to approximate setup accuracy, and vector magnitudes for these shifts were calculated. Setup group mean, interpatient, interinstitution, and random error were estimated, and clinical factors were compared by mixed linear modeling. RESULTS: Among 96 patients, with 2179 pretreatment cone-beam computed tomography acquisitions, median age was 9 years (1-20). Setup parameters were 3.13, 3.02, 1.64, and 1.48 mm for vector magnitude group mean, interpatient, interinstitution, and random error, respectively. On multivariable analysis, there were no significant differences in mean vector magnitude by age, gender, performance status, target location, extent of resection, chemotherapy, or steroid or anesthesia use. Providers rated >99% of images as adequate or better for target localization. CONCLUSIONS: A lower-dose cone-beam computed tomography protocol demonstrated table shift vector magnitude that approximate clinical target volume/planning target volume expansions used in central nervous system radiotherapy. There were no significant clinical predictors of setup accuracy identified, supporting use of this lower-dose cone-beam computed tomography protocol across a diverse pediatric population with brain tumors.

Reirradiation for Recurrent Pediatric Central Nervous System Malignancies: A Multi-institutional Review.

PURPOSE: Reirradiation has been proposed as an effective modality for recurrent central nervous system (CNS) malignancies in adults. We evaluated the toxicity and outcomes of CNS reirradiation in pediatric patients. METHODS AND MATERIALS: The data from pediatric patients <21 years of age at the initial diagnosis who developed a recurrent CNS malignancy that received repeat radiation therapy (RT) across 5 facilities in an international pediatric research consortium were retrospectively reviewed. RESULTS: Sixty-seven pediatric patients underwent CNS reirradiation. The primary diagnoses included medulloblastoma/primitive neuroectodermal tumor (n=20; 30%), ependymoma (n=19; 28%), germ cell tumor (n=8; 12%), high-grade glioma (n=9; 13%), low-grade glioma (n=5; 7%), and other (n=6; 9%). The median age at the first course of RT was 8.5 years (range 0.5-19.5) and was 12.3 years (range 3.3-30.2) at reirradiation. The median interval between RT courses was 2.0 years (range 0.3-16.5). The median radiation dose and fractionation in equivalent 2-Gy fractions was 63.7 Gy (range 27.6-74.8) for initial RT and 53.1 Gy (range 18.6-70.1) for repeat RT. The relapse location was infield in 52 patients (78%) and surrounding the initial RT field in 15 patients (22%). Thirty-seven patients (58%) underwent gross or subtotal resection at recurrence. The techniques used for reirradiation were intensity modulated RT (n=46), 3-dimensional conformal RT (n=9), stereotactic radiosurgery (n=4; 12-13 Gy × 1 or 5 Gy × 5), protons (n=4), combined modality (n=3), 2-dimensional RT (n=1), and brachytherapy (n=1). Radiation necrosis was detected in 2 patients after the first RT course and 1 additional patient after reirradiation. Six patients (9%) developed secondary neoplasms after initial RT (1 hematologic, 5 intracranial). One patient developed a secondary neoplasm identified shortly after repeat RT. The median overall survival after completion of repeat RT was 12.8 months for the entire cohort and 20.5 and 8.4 months for patients with recurrent ependymoma and medulloblastoma after reirradiation, respectively. CONCLUSIONS: CNS reirradiation in pediatric patients could be a reasonable treatment option, with moderate survival noted after repeat RT. However, prospective data characterizing the rates of local control and toxicity are needed.

Practice patterns of photon and proton pediatric image guided radiation treatment: results from an International Pediatric Research consortium.

PURPOSE: Image guided radiation therapy (IGRT) has become common practice for both photon and proton radiation therapy, but there is little consensus regarding its application in the pediatric population. We evaluated clinical patterns of pediatric IGRT practice through an international pediatrics consortium comprised of institutions using either photon or proton radiation therapy. METHODS AND MATERIALS: Seven international institutions with dedicated pediatric expertise completed a 53-item survey evaluating patterns of IGRT use in definitive radiation therapy for patients ≤21 years old. Two institutions use proton therapy for children and all others use IG photon therapy. Descriptive statistics including frequencies of IGRT use and means and standard deviations for planning target volume (PTV) margins by institution and treatment site were calculated. RESULTS: Approximately 750 pediatric patients were treated annually across the 7 institutions. IGRT was used in tumors of the central nervous system (98%), abdomen or pelvis (73%), head and neck (100%), lung (83%), and liver (69%). Photon institutions used kV cone beam computed tomography and kV- and MV-based planar imaging for IGRT, and all proton institutions used kV-based planar imaging; 57% of photon institutions used a specialized pediatric protocol for IGRT that delivers lower dose than standard adult protocols. Immobilization techniques varied by treatment site and institution. IGRT was utilized daily in 45% and weekly in 35% of cases. The PTV margin with use of IGRT ranged from 2 cm to 1 cm across treatment sites and institution. CONCLUSIONS: Use of IGRT in children was prevalent at all consortium institutions. There was treatment site-specific variability in IGRT use and technique across institutions, although practices varied less at proton facilities. Despite use of IGRT, there was no consensus of optimum PTV margin by treatment site. Given the desire to restrict any additional radiation exposure in children to instances where the exposure is associated with measureable benefit, prospective studies are warranted to optimize IGRT protocols by modality and treatment site.