John T. Lucas

Vismodegib and Physeal Closure in a Pediatric Patient

To the Editor: A 2-year-old female presented with several weeks history of suboccipital headaches. Brain magnetic resonance imaging (MRI) revealed hydrocephalus and a large lateralized posterior fossa mass (Fig. 1A). She underwent a gross total resection that confirmed aWHOGrade 4 nodular desmoplastic medulloblastoma, Sonic Hedgehog subtype. Due to her young age, shewas treated on an institutional protocol with chemotherapy to delay adjuvant radiation. She completed induction and consolidation chemotherapy but developed intracranial and thoracic spine leptomeningeal disease 3 months into the maintenance phase of oral chemotherapy. She was started on vismodegib with evidence of treatment response on interval MRI at both 1 and 3 months after start of therapy. Four months into therapy with vismodegib, she developed bilateral knee pain that was evaluatedwith frontal and lateral radiographs of both knees. Physeal fusion of both the proximal tibial growth plates was noted relative to a pre-vismodegib imaging evaluation (Fig. 1B). On subsequent radiographic evaluation 3months later, the distal femoral growth plates were also noted to have signs of premature fusion. Reimaging of the tibial and distal femoral growth

Late toxicity and outcomes following radiation therapy for chest wall sarcomas in pediatric patients

PURPOSE To investigate the contribution of radiation therapy to acute and late toxicity in pediatric chest wall sarcoma patients and evaluate dosimetric correlates of higher incidence toxicities such as scoliosis and pneumonitis. METHODS AND MATERIALS The data from 23 consecutively treated pediatric patients with chest wall sarcomas of various histologies (desmoid, Ewing, rhabdomyosarcoma, nonrhabdomyosarcoma-soft tissue sarcomas) were reviewed to evaluate the relationship between end-organ radiation dose, clinical factors, and the risk of subsequent late effects (scoliosis, pneumonitis). Cobb angles were used to quantify the extent of scoliosis. Doses to the spine and lung were calculated from the radiation treatment plan. RESULTS The range of scoliosis identified on follow-up imaging ranged from -47.6 to 64° (median, 2.95°). No relationship was identified between either radiation dose to the ipsilateral or contralateral vertebral body or tumor size and the degree or direction of scoliosis. The extent of surgical resection and number and location of resected ribs affected the extent of scoliosis. The dominant predictor of extent of scoliosis at long-term follow-up was the extent of scoliosis following surgical resection. Radiation pneumonitis was uncommon and was not correlated with mean dose or volume of lung receiving 24 Gy; however, 1 of 3 surviving patients who received whole pleural surface radiation therapy developed significant restrictive lung disease. CONCLUSIONS Acute and late radiation therapy-associated toxicities in pediatric chest wall sarcoma patients are modest. The degree of scoliosis following resection is a function of the extent of resection and of the number and location of ribs resected, and the degree of scoliosis at the last follow-up visit is a function of the extent of scoliosis following surgery. Differential radiation therapy dose across the vertebral body does not increase the degree of scoliosis. Severe restrictive pulmonary disease is a late complication of survivors after whole pleural surface radiation therapy.

Radiomics Features Differentiate Between Normal and Tumoral High-Fdg Uptake.

Identification of FDGavid- neoplasms may be obscured by high-uptake normal tissues, thus limiting inferences about the natural history of disease. We introduce a FDG-PET radiomics tissue classifier for differentiating FDGavid- normal tissues from tumor. Thirty-three scans from 15 patients with Hodgkin lymphoma and 68 scans from 23 patients with Ewing sarcoma treated on two prospective clinical trials were retrospectively analyzed. Disease volumes were manually segmented on FDG-PET and CT scans. Brain, heart, kidneys and bladder and tumor volumes were automatically segmented on PET images. Standard-uptake-value (SUV) derived shape and first order radiomics features were computed to build a random forest classifier. Manually segmented volumes were compared to automatically segmented tumor volumes. Classifier accuracy for normal tissues was 90%. Classifier performance was varied across normal tissue types (brain, left kidney and bladder, hear and right kidney were 100%, 96%, 97%, 83% and 87% respectively). Automatically segmented tumor volumes showed high concordance with the manually segmented tumor volumes (R2 = 0.97). Inclusion of texture-based radiomics features minimally contributed to classifier performance. Accurate normal tissue segmentation and classification facilitates accurate identification of FDGavid tissues and classification of those tissues as either tumor or normal tissue.

Factors influencing risk-based care of the childhood cancer survivor in the 21st century

The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient‐specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment‐related toxicity and possible targets for intervention in this population. Furthermore, although current long‐term follow‐up guidelines comprehensively address specific therapy‐related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment‐related health risk and evolving treatment approaches, a patient‐centered and risk‐adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133‐152.

Managing local-regional failure in children with high-risk neuroblastoma: A single institution experience

Intensification of systemic therapy for high‐risk neuroblastoma (HRNB) has resulted in improved local control and overall survival (OS) leaving potential for de‐escalation of primary site radiotherapy. The utility of primary site de‐escalation should be evaluated in the context of potential for successful local‐regional salvage. We evaluated salvage strategies and outcomes in patients with HRNB with local‐regional recurrence as a component of first failure.

The Non-rhabdomyosarcoma Soft Tissue Sarcomas, Desmoid Tumor and Osteosarcoma

Soft-tissue sarcoma (STS) are a group of rare tumors diagnosed in children and adults that require multi-modality specialty care. The etiology of STS in children is largely unknown although they are among the tumor types associated with cancer predisposition syndromes and included in the differential of radiation-induced malignancies. STS include a broad variety of histologic subtypes, diverse presentations, and wide-ranging lethality. Evaluation and management of STS in pediatric patients has evolved based on knowledge derived from clinical trials performed in adults and more recently prospective studies performed exclusively with children. Surgery, irradiation modalities, and conventional chemotherapy have identified roles in the treatment of pediatric patients with current studies focused on toxicity reduction in low-risk patients, optimal sequencing of therapy and new agent testing in intermediate and high-risk patients, and systematic salvage strategies for patients that do not respond to front-line therapy.

Prior non-irradiative focal therapies do not compromise the efficacy of delayed episcleral plaque brachytherapy in retinoblastoma

Background/aims Non-irradiative local therapies have shown promise in delaying or supplanting external beam radiotherapy (EBRT) and enucleation in patients with retinoblastoma. We hypothesised that prior focal therapy does not compromise the efficacy of delayed episcleral plaque brachytherapy (epBRT). Methods We performed an institutional review board-approved medical record review of patients with retinoblastoma who were treated with I-125 epBRT prior to (primary) or following chemoreduction (delayed), alone and in combination with non-irradiative focal therapy. Clinical and treatment characteristics were retrieved. Treatment failure was defined as the need for subsequent EBRT and/or enucleation. Event-free and ocular survival rates were calculated from the date of plaque placement. The cumulative incidences (CIs) of treatment failure and enucleation were compared across strata using Gray’s test. Results We identified 50 patients with retinoblastoma (54 eyes), who received a total of 56 plaques between January 1986 and December 2010, with a median follow-up of 8.3 years (range, 0.8–21.2 years). The median time from diagnosis to plaque placement was 12.7 months (range, 0.1–128 months). The CI and 95% CI of treatment failure and enucleation following epBRT at 5 years was 37%±7.2% and42.2%±7.3%, respectively. The lack of prior diode or green laser therapy was predictive of increased risk for treatment failure (p=0.02 and 0.03). International Classification group C or D was predictive of decreased time to enucleation (p=0.004). The use of any focal therapy was not predictive of time to treatment failure (p=0.33). Conclusions The use of non-irradiative focal therapies prior to or following epBRT does not decrease the time to enucleation or treatment failure.

Rapid and fulminant leptomeningeal spread following radiotherapy in diffuse intrinsic pontine glioma

A 4‐year‐old male presented with rapid‐onset cranial nerve palsy and ataxia. Brain magnetic resonance imaging (MRI) revealed a pontine mass lesion with discordant conventional and advanced imaging. A stereotactic core biopsy revealed glioblastoma with immunostaining suggestive of histone H3K27M and TP53 mutation, consistent with diffuse intrinsic pontine glioma. MRI 3 months after radiotherapy revealed extensive new leptomeningeal metastatic disease involving both the supra‐ and infratentorial brain, as well as the imaged portion of the spine. Tissue procured at the time of needle biopsy has undergone striking in vivo expansion as an orthotopic xenograft.

SU-D-207A-06: Pediatric Abdominal Organ Motion Quantified Via a Novel 4D MRI Method

PURPOSE To develop a 4D MRI method for assessing respiration-induced abdominal organ motion in children receiving radiation therapy. METHODS A 4D MRI using internal image-based respiratory surrogate has been developed and implemented on a clinical scanner (1.5T Siemens Avanto). Ten patients (younger group: N=6, 2-5 years, anesthetized; older group: N=4, 11-15 years) with neuroblastoma, Wilms tumor rhabdomyosarcoma, or desmoplastic small round cell tumor received free breathing 4D MRI scans for treatment planning. Coronal image slices of the entire abdomen were retrospectively constructed in 10 respiratory phases. A B-spline deformable registration (Metz et al. 2011) was performed on 4D datasets to automatically derive motion trajectories of selected anatomical landmarks, including the dome and the center of the liver, and the superior edges of kidneys and spleen. The extents of the motion in three dimensions (anteroposterior, AP; mediolateral, ML; superoinferior, SI) and the correlations between organ motion trajectories were quantified. RESULTS The 4D MRI scans were successfully performed in <20 minutes for all patients without the use of any external device. Organ motion extents were larger in adolescents (kidneys: 3-13 mm SI, liver and spleen: 6-18 mm SI) than in younger children (kidneys:<3mm in all directions; liver and spleen: 1-8 mm SI, 1-5 mm ML and AP). The magnitude of respiratory motion in some adolescents may warrant special motion management. Motion trajectories were not synchronized across selected anatomical landmarks, particularly in the ML and AP directions, indicating inter- and intra-organ variations of the respiratory-induced motion. CONCLUSION The developed 4D MRI acquisition and motion analysis methods provide a non-ionizing, non-invasive approach to automatically measure the organ motion trajectory in the pediatric abdomen. It is useful for defining ITV and PRV, monitoring changes in target motion patterns during the treatment course, and studying interplay effects in proton scanning.

Predictors for readmission after pancreatic resection for malignancy.

301 Background: Readmission after pancreatic resection has been reported as high as 50%. This study was undertaken to determine factors predicting readmission after pancreatic resection for malignancy. Methods: We reviewed the medical records of 202 patients to identify patients that had a pancreatic resection for malignancy between 2003 and 2010. Outcome measures included patient characteristics, medical comorbidities, and perioperative factors. Results: A total of 202 patients underwent pancreatic resection for malignancy. AJCC T stage was T1, T2, T3, and T4 in 10.9%, 26.3%, 52% and 9.2% respectively. Pancreatic head malignancies made up 84.8% of the patients, 2.3% were pancreatic neck, 8.4% were pancreatic body, and 4.5% were pancreatic tail primaries. Preoperative biliary stents were placed in 58% of patients. Adjuvant radiation and chemotherapy were given in 47.8 and 61.39% respectively. The readmission rate following resection was 20% at 60 days. The most common reasons for readmission within 60 day...