Sensitization of Endothelial Cells to Ionizing Radiation Exacerbates Delayed Radiation Myelopathy in Mice

Delayed radiation myelopathy is a rare, but significant late side effect from radiation therapy that can lead to paralysis. The cellular and molecular mechanisms leading to delayed radiation myelopathy are not completely understood but may be a consequence of damage to oligodendrocyte progenitor cells and vascular endothelial cells. Here, we aimed to determine the contribution of endothelial cell damage to the development of radiation-induced spinal cord injury using a genetically defined mouse model in which endothelial cells are sensitized to radiation due to loss of the tumor suppressor p53. Tie2Cre; p53FL/+ and Tie2Cre; p53FL/– mice, which lack one and both alleles of p53 in endothelial cells, respectively, were treated with focal irradiation that specifically targeted the lumbosacral region of the spinal cord. The development of hindlimb paralysis was followed for up to 18 weeks after either a 26.7 Gy or 28.4 Gy dose of radiation. During 18 weeks of follow-up, 83% and 100% of Tie2Cre; p53FL/– mice developed hindlimb paralysis after 26.7 and 28.4 Gy, respectively. In contrast, during this period only 8% of Tie2Cre; p53FL/+ mice exhibited paralysis after 28.4 Gy. In addition, 8 weeks after 28.4 Gy the irradiated spinal cord from Tie2Cre; p53FL/– mice showed a significantly higher fractional area positive for the neurological injury marker glial fibrillary acidic protein (GFAP) compared with the irradiated spinal cord from Tie2Cre; p53FL/+ mice. Together, our findings show that deletion of p53 in endothelial cells sensitizes mice to the development of delayed radiation myelopathy indicating that endothelial cells are a critical cellular target of radiation that regulates myelopathy.

Bone infarct (osteonecrosis) as late side effect of steroid in acute lymphoblastic leukemia survivor

Survivors of acute lymphoblastic leukemia (ALL), though cured of their primary disease may suffer from long-term complications such as bone infarction contributing to a major morbidity. Here, we report a very rare case of bone infarct in bilateral tibia and femur of a patient of acute lymphoblastic leukemia, post completion of maintenance chemotherapy. With this case report, we suggest that appropriate preventive measures are necessary to decrease the risk of this very rare morbidity.

Hypothyroidism and its impact on outcomes in head and neck cancer.

e24066 Background: Hypothyroidism is a known late side effect of chemo-radiation in head and neck cancer. Hypothyroidism has been known to be associated with improved outcomes in renal cell carcinoma. Whether such a phenomenon exists in head and neck cancer is unknown. Methods: We performed a phase 3 study evaluating the role of Nimotuzumab in head and neck squamous cell cancers (HNSCC). In this study adult HNSCC patients treated with Cisplatin and radiation were randomly assigned to receive Nimotuzumab or not. The data of this study has been utilized for this analysis. Hypothyroidism was defined as TSH level more than 4.95 U/L. The cumulative incidence of hypothyroidism and its impact on PFS (progression free survival), OS (overall survival) and loco-regional control (LRC) was evaluated using binary regression analysis. To study the impact of hypothyroidism in outcomes a landmark analysis was performed. Results: 176/536 patients analyzed developed hypothyroidism with a cumulative incidence of 33%. Hypothyroidism showed a favorable impact on PFS, OS and LRC. Median PFS was 19.5 months while median OS was 22.2 months in the euthyroid subgroup vs not reached (NR) for both in the hypothyroid subgroup. The respective hazard rates (HR) for PFS and OS was 0.37 (95% CI: 0.27 - 0.52) and 0.15 (95% CI: 0.11 - 0.23). The LRC was also better with its median duration being 39.2 months vs NR in the euthyroid and hypothyroid subgroups respectively; HR for LRC being 0.40 (95% CI: 0.28 - 0.58). Conclusions: Thus development of hypothyroidism is associated with improved outcomes in HNSCC in terms of LRC and survival.

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

Atomic in vivo nanogenerators such as actinium-225, thorium-227, and radium-223 are of increasing interest and importance in the treatment of patients with metastatic cancer diseases. This is due to their peculiar physical, chemical, and biological characteristics, leading to astonishing responses in otherwise resistant patients. Nevertheless, there are still a few obstacles and hurdles to be overcome that hamper the broader utilization in the clinical setting. Next to the limited supply and relatively high costs, the in vivo complex stability and the fate of the recoiling daughter radionuclides are substantial problems that need to be solved. In radiobiology, the mechanisms underlying treatment efficiency, possible resistance mechanisms, and late side effect occurrence are still far from being understood and need to be unraveled. In this review, the current knowledge on the scientific and clinical background of targeted alpha therapies is summarized. Furthermore, open issues and novel approaches with a focus on the future perspective are discussed. Once these are unraveled, targeted alpha therapies with atomic in vivo nanogenerators can be tailored to suit the needs of each patient when applying careful risk stratification and combination therapies. They have the potential to become one of the major treatment pillars in modern cancer management.

Deep radiation-induced ulcer following nasopharyngeal carcinoma: surgical management

Nasopharyngeal carcinoma (NPC), an uncommon malignancy in Western Countries and Radiotherapy, remains an effective treatment. Its side effects are classified as either immediate or late; postradiation necrosis is as an important late side effect with a strong impact on the prognosis in patients with NPC. We report the case of 65-year-old Caucasian man presenting with a deep necrotic ulcer of the nasopharynx and osteoradionecrosis of the skull base that appeared 3 months after radiotherapy for nasopharyngeal carcinoma. Conservative treatment was applied with surgical management of the ulcer. Clinical and radiological outcomes are presented. Radiotherapy remains a good treatment option with varying degrees of side effects, in particular, postradiation necrosis and ulcer. Multiple options of treatment have been described. However, the surgical management could be indicated in cases of deep ulcer with life-threatening prognosis.

Unilateral vocal cord paralysis in squamous cell lung cancer treated with stereotactic body radiation therapy

AimWe report a unique presentation of a late side effect associated with stereotactic body radiation therapy (SBRT) of the lung.SummaryThe case of a 65-year-old male who developed left-sided vocal cord paralysis after two courses of SBRT for squamous cell lung carcinoma is presented. The patient developed this late toxicity 15 months after his second treatment, which was to address a recurrence in the perihilar region of the left upper lobe.