A GdW10@PDA-CAT Sensitizer with High-Z Effect and Self-Supplied Oxygen for Hypoxic-Tumor Radiotherapy

Anticancer treatment is largely affected by the hypoxic tumor microenvironment (TME), which causes the resistance of the tumor to radiotherapy. Combining radiosensitizer compounds and O2 self-enriched moieties is an emerging strategy in hypoxic-tumor treatments. Herein, we engineered GdW10@PDA-CAT (K3Na4H2GdW10O36·2H2O, GdW10, polydopamine, PDA, catalase, CAT) composites as a radiosensitizer for the TME-manipulated enhancement of radiotherapy. In the composites, Gd (Z = 64) and W (Z = 74), as the high Z elements, make X-ray gather in tumor cells, thereby enhancing DNA damage induced by radiation. CAT can convert H2O2 to O2 and H2O to enhance the X-ray effect under hypoxic TME. CAT and PDA modification enhances the biocompatibility of the composites. Our results showed that GdW10@PDA-CAT composites increased the efficiency of radiotherapy in HT29 cells in culture. This polyoxometalates and O2 self-supplement composites provide a promising radiosensitizer for the radiotherapy field.

Analysis of Geometric and Dosimetric Effects of Bra Application to Support Large or Pendulous Breasts During Radiotherapy Planning: A Retrospective Single-Center Study

Purpose: To evaluate geometric and dosimetric effects of bra application during radiotherapy planning for breast cancer patients with large and pendulous breasts. Materials and Methods: Twenty patients with chest sizes >38 inches between April 2019 and July 2019 underwent radiotherapy planning with and without a radiation bra (Chabner XRT®). Geometric and dosimetric parameters included the breast volume, superior-inferior (SI) distance, separation (S) as the distance of the longest diameter of the clinical target volume (CTV), conformity number (CN), and homogeneity index (HI) of CTV. The organs at risk (OARs) were defined as the lungs, heart, and liver. Results: The use of the radiation bra provided mean changes of −0.51 cm for S, −1.45 cm for SI, and −61.18 cc for breast volume (all P < 0.05). Breast volume was correlated with bra-related changes in cross diameter (r = 0.641, P = 0.002) and volume (r = 0.680, P = 0.001). Significant dose reductions were observed for the lungs (mean V10: 19.58 cc, V20: 17.13 cc, Dmean: 86.24 cGy) and heart (Dmean: 170.23 cGy). No significant differences were observed for CN (0.62-0.67) and HI (0.19-0.20) of the CTV. Conclusion: The application of a radiation bra was associated with better geometric and dosimetric planning parameters, with a smaller CTV and lower doses to the OARs (lungs and heart) in the radiotherapy field. In addition, we expect that bra use during radiotherapy would provide emotional benefits.

RARE-12. VASCULOPATHY IN PEDIATRIC CRANIOPHARYNGIOMA PATIENTS TREATED WITH SURGERY AND RADIOTHERAPY

PURPOSE As much as 40% of pediatric brain tumor patients will experience varied levels of Vasculopathy (VS), however few predictive factors have been described. Here we describe the type and timing of VS and explore the relationship between treatment modality and the timing, location, and distribution of VS. METHODS 94 pediatric Craniopharyngioma patients underwent surgery and proton radiotherapy. Pre- and post-treatment imaging, cumulative physical and biological proton dose maps, clinical characteristics, and measures of dyslipidemia were evaluated. MR and MRAs were evaluated for pre- and post-radiotherapy VS (type, workup, location, and severity). VS events were segmented and described according to their normal brain region, and vascular territory. RESULTS 47 patients were found to have 154 confirmed VS of varying severity with a median time to event of 3.41 years 95% CI 3.08–3.88. 22% (N=21) of patients had ≥1 pre-existing instances of VS and 26.6% (N=25) had a dyslipidemia at diagnosis. Forty-six (48.9%) patients had evidence of VS post-RT with 9.5% (N=9) being clinically significant. Aspirin was recommended in 10.6% (N=10) patients. Only 4 (4.2%) patients required revascularization. Clinical characteristics were not predictive of VS. An increased frequency of VS were observed along the operative corridor and high-dose radiotherapy field. CONCLUSIONS VS often precedes radiotherapy necessitating appropriate baseline imaging. Surgery type and extent are interrelated to the risk for radiotherapy-induced VS. While the spatial radiotherapy dose distribution approximated most vascular injury events, it was not all-inclusive. Spatial modeling of biological and physical dose may offer insights into therapy related vascular injury.

NIMG-67. DISAPPEARING DOTS – TRANSIENT LATE ENHANCING LESIONS YEARS AFTER BRAIN RADIOTHERAPY

BACKGROUND Late-delayed radiation effects appear 6 months to years following radiotherapy. We characterize a species of small enhancing lesions in the late-delayed phase of post-radiotherapy that are distinct from the classic descriptions of radiation necrosis or pseudoprogression associated with mass effect and edema. These “disappearing dots” are small, do not exert mass effect nor edema, and spontaneously resolve. METHOD We retrospectively describe a series of cases with “disappearing dots” following brain radiotherapy. RESULTS There were 10 cases (4 men), median age 42 years (range 29-63). Diagnoses were glioblastoma (3); low grade astrocytoma, anaplastic astrocytoma, and anaplastic oligodendroglioma (2 each); and solitary fibrous tumor (1). All patients received 54-60 Gy (Gray) of external beam radiotherapy, except one (proton beam therapy to 60 cobalt Gray equivalent). Disappearing dots appeared at a median of 27 months (range 5-197) post-radiotherapy. Lesions were relatively small (~&lt; 1 cm3), peri-ventricular, and within the radiotherapy field. Most enlarged before resolving. Advanced MR imaging and fluorodeoxyglucose (FGD)-PET results were inconsistent. Lesions persisted a median of 8.5 months (range 1-49) before spontaneous resolution. All were asymptomatic. Biopsy in one case revealed treatment effects rather than recurrent tumor. CONCLUSIONS Asymptomatic small periventricular enhancing lesions can develop and remit spontaneously, years following brain radiotherapy. Such disappearing dots should be part of the differential diagnosis along with tumor recurrence. of new enhancing lesions in the late-delayed phase post-radiotherapy.

Bone and Soft‐Tissue Sarcoma Risk in Long‐Term Survivors of Hereditary Retinoblastoma Treated With Radiation

PURPOSE Survivors of hereditary retinoblastoma have excellent survival but substantially increased risks of subsequent bone and soft-tissue sarcomas, particularly after radiotherapy. Comprehensive investigation of sarcoma risk patterns would inform clinical surveillance for survivors. PATIENTS AND METHODS In a cohort of 952 irradiated survivors of hereditary retinoblastoma who were originally diagnosed during 1914 to 2006, we quantified sarcoma risk with standardized incidence ratios (SIRs) and cumulative incidence analyses. We conducted analyses separately for bone and soft-tissue sarcomas occurring in the head and neck (in/near the radiotherapy field) versus body and extremities (out of field). RESULTS Of 105 bone and 124 soft-tissue sarcomas, more than one half occurred in the head and neck (bone, 53.3%; soft tissue, 51.6%), one quarter in the body and extremities (bone, 29.5%; soft tissue, 25.0%), and approximately one fifth in unknown/unspecified locations (bone, 17.1%; soft tissue, 23.4%). We noted substantially higher risks compared with the general population for head and neck versus body and extremity tumors for both bone (SIR, 2,213; 95% CI, 1,671 to 2,873 v SIR, 169; 95% CI, 115 to 239) and soft-tissue sarcomas (SIR, 542; 95% CI, 418 to 692 v SIR, 45.7; 95% CI, 31.1 to 64.9). Head and neck bone and soft-tissue sarcomas were diagnosed beginning in early childhood and continued well into adulthood, reaching a 60-year cumulative incidence of 6.8% (95% CI, 5.0% to 8.7%) and 9.3% (95% CI, 7.0% to 11.7%), respectively. In contrast, body and extremity bone sarcoma incidence flattened after adolescence (3.5%; 95% CI, 2.3% to 4.8%), whereas body and extremity soft-tissue sarcoma incidence was rare until age 30, when incidence rose steeply (60-year cumulative incidence, 6.6%; 95% CI, 4.1% to 9.2%), particularly for females (9.4%; 95% CI, 5.1% to 13.8%). CONCLUSION Strikingly elevated bone and soft-tissue sarcoma risks differ by age, location, and sex, highlighting important contributions of both radiotherapy and genetic susceptibility. These data provide guidance for the development of a risk-based screening protocol that focuses on the highest sarcoma risks by age, location, and sex.