Oral administration of 3,3'-diselenodipropionic acid prevents thoracic radiation induced pneumonitis in mice by suppressing NF-kB/IL-17/G-CSF/neutrophil axis.

The incidence of symptomatic radiation induced lung pneumonitis (RILP), a major dose limiting side effect of thoracic radiotherapy, is in the range of 15-40%. Therapeutic options for the prevention and treatment of RILP are limited. Hence there is a need for developing novel radioprotectors to prevent RILP which can be patient compliant. This study sought to evaluate the efficacy of oral 3,3'-diselenodipropionic acid (DSePA), a novel selenocystine derivative to prevent RILP. C3H/HeJ (pneumonitis responding) mice received a single dose of 18 Gy, whole thorax irradiation and a subset were treated with DSePA orally (2.5 mg/kg), three times per week beginning 2 h post irradiation and continued till 6 months. DSePA delayed onset of grade ≥ 2 RILP by 45 days compared to radiation control (~105 versus ~60 days). It also reversed the severity of pneumonitis in 3/10 radiation treated mice leading to significant improvement in asymptomatic survival compared to radiation control (~180 versus ~102 days). DSePA significantly (p < 0.05) reduced the radiation-mediated infiltration of polymorphonuclear neutrophils (PMN) and elevation in levels of cytokines such as IL1-ß, ICAM-1, E-selectin, IL-17 and TGF-ß in the bronchoalveolar lavage fluid. Moreover DSePA lowered PMN-induced oxidants, maintained glutathione peroxidase activity and suppressed NF-kB/IL-17/G-CSF/neutrophil axis in the lung of irradiated mice. Additionally, this compound did not protect A549 (lung cancer) derived xenograft tumor from radiation exposure in SCID mice. DSePA offers protection to normal lung against RILP without affecting radiation sensitivity of tumors. It has the potential to be developed as an oral agent for preventing RILP.

Local therapy in non-metastatic primary Ewing sarcoma of the mandible and maxilla in children.

Ewing sarcoma (ES) of the jaw bones comprises a small fraction of ES at all sites. Due to their rarity, a specific policy for local treatment is lacking. The aim of this study was to evaluate the local therapy for ES and recommend measures to individualize treatment options. Patients with primary non-metastatic ES of the jaw bones treated between August 2005 and February 2015 were analyzed. All patients received primary induction chemotherapy, following which lesions amenable to resection based on specific radiological criteria were resected; those with unresectable lesions were offered definitive radiotherapy. The maxilla was the primary site in 13 patients and the mandible in eight. The median age of patients was 11.6 years (range 5-17 years). Overall, surgery was performed in 17 patients and definitive radiotherapy was used in four patients. Postoperative radiotherapy was administered to 12 patients and was avoided in five patients with 100% tumour necrosis. The 3-year overall survival, event-free survival, and local control were 68.1%, 63.6%, and 80.2%, respectively. Mandible primary and a histological response to chemotherapy were significant prognostic factors. The stratification of patients based on radiological criteria aids in selecting local therapy. In eligible patients, surgery with contemporary reconstruction results in optimal oncological and functional outcomes. Surgery also has the added advantage of identifying patients who may not need radiotherapy.

Prospective observational study on diagnostic accuracy of whole-body MRI in solid small round cell tumours.

AIM: To assess the diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) for metastatic disease in patients with solid small round cell tumours (SRCT) by comparing it with routine staging procedures (standard of care). MATERIALS AND METHODS: Eligible cases of neuroblastoma, primitive neuroectodermal tumour, and rhabdomyosarcoma were enrolled in the study after obtaining informed consent. WB-MRI was undertaken using overlapping coronal T1 and short-tau inversion recovery (STIR) sequences. Lesions were classified into skeletal, pulmonary, and soft-tissue types. Conventional staging, which consisted of combined positron-emission tomography & computed tomography (PET-CT), bone scintigraphy & bone marrow biopsy for bone metastases, CT thorax for lung metastases, combined PET-CT, metaiodobenzylguanidine (MIBG) scintigraphy (in neuroblastoma) for soft tissue metastases and clinical evaluation was used as the reference standard. Parameters for diagnostic accuracy were calculated. RESULTS: Thirty-four out of forty patients enrolled were included in final analysis, half of them having metastatic disease. The sensitivity, specificity, positive and negative predictive value, and the diagnostic accuracy of WB-MRI and PET-CT for skeletal metastases as compared to reference standard were 91.9%, 99.8%, 97.4%, 99.6%, and 95.5% and 99.1%, 99.9%, 99.1%, 99.9%, and 99.9%, respectively. The sensitivity of MRI, only PET and PET-CT with plain CT thorax was 30%, 40%, and 100%, respectively, for lung metastases. The sensitivity of MRI for soft-tissue lesions was 76.9%. CONCLUSION: WB-MRI is a radiation-free tool with high diagnostic accuracy for the evaluation of metastatic disease to the marrow. The rate of detection of soft-tissue metastases, such as nodal metastases, is less when WB-MRI is compared with conventional staging using coronal STIR images. CT thorax is essential for accurate evaluation of lung metastases.

Understanding the principles in management of Wilms' tumour: can imaging assist in patient selection?

The management of Wilms' tumour has evolved through thorough systematic research, predominantly lead by two groups: the Wilms' Tumour Study Committee of the International Society of Paediatric Oncology (SIOP) and National Wilms' Tumor Study Group (NWTSG) of North America. These two groups differ in their approach: SIOP advocates initial chemotherapy of 4-6 weeks followed by surgery, whereas the NWTSG advocates upfront surgery, with certain exceptions. This review briefly discusses the principles, and pros and cons of each approach. Both the treatment approaches have equivalent outcomes (in the form of event-free survival and overall survival), when compared stage-wise. With this knowledge, modern imaging can be used for individualizing treatment in anticipation of minimizing complications. The review identifies critical imaging features and discusses the reliability of imaging based on current reports in the literature.