RT leads to hypocellularity, hypovascularity, and hypoxia of treated tissues, resulting in a reduced ability for growth and healing. Studies demonstrate that irradiated bone contains fewer osteoblast cells and osteocytes than unirradiated bone, resulting in reduced regenerative capacity.12,13 Furthermore, the reconstruction of bony defects resulting after cancer treatment has been shown to be difficult and associated with a high risk of complications.14 Given the impaired ability of irradiated bone to regenerate, studies have evaluated the use of growth factors and gene therapy to promote bone formation after treatment.15 Bone marrow stem cells have been shown to reverse radiation-induced cellular depletion and to increase osteocyte counts in animal studies.12 Further, overexpression of miR-34a, a tumor suppressor involved in tissue development, has been shown to improve osteoblastic differentiation of irradiated bone marrow stem cells and promote bone regeneration in vitro and in animal studies.13 While several techniques are being studied in vitro and in animal studies to promote bony regeneration after RT, there is a lack of data on use of these techniques in humans with cancer.
With our case, there was great uncertainty related to the ability of bone to regenerate during treatment and concern regarding consequences of formation of a skull base defect during treatment. CT imaging revealed bony regeneration of the central skull base and clivus, as well as occipital condyles, that occurred throughout the RT course. There was clear evidence of bone regeneration on the replanning CT obtained 5 weeks after treatment initiation. To our knowledge, this is the first report to demonstrate rapid bony regeneration during RT, thereby maintaining the integrity of the skull base and precluding the need for neurosurgical intervention. Moving forward, imaging should be considered during treatment for patients with tumor-related destruction of the skull base and upper cervical spine to evaluate the extent of bony regeneration during treatment and estimate the potential risk of craniocervical instability. Further studies with imaging during treatment are needed for more information on the likelihood of bony regeneration and factors that correlate with bony regeneration during treatment. As in other reports, our case demonstrates that bony regeneration may predict complete response to RT.9
Our patient’s tumor was HPV-positive and EBV-negative. In the US, the rate of HPV-positive NPC is 35%.16 However, HPV-positive NPC is much less common in endemic areas. A recent study from China of 1,328 patients with NPC revealed a 6.4% rate of HPV-positive/EBV-negative cases.17 In that study, patients with HPV-positive/EBV-negative tumors had improved survival compared to patients whose tumors were HPV-negative/EBV-positive. Another study suggests that the impact of HPV in NPC varies according to race, with HPV-positivity predicting for improved outcomes in East Asian patients and worse outcomes in White patients.17 A study from the University of Michigan suggests that both HPV-positive/EBV-negative and HPV-negative/EBV-negative NPC are associated with worse overall survival and locoregional control than EBV-positive NPC.2 Overall, the prognostic role of HPV in NPC remains unclear given conflicting information in the literature and the lack of large population studies.18
Conclusions
There is a paucity of literature on bony regeneration in patients with skull base destruction from advanced NPC, and in particular, the ability of skull base regeneration to occur during treatment simultaneous with tumor regression. Our patient had HPV-positive/EBV-negative NPC, but it is unclear how this subtype affected his prognosis. Factors such as tumor histology, radiosensitivity with rapid tumor regression, and young age may have all contributed to the rapidity of bone regeneration in our patient. This case report demonstrates that an impressive tumor response to chemoradiation with simultaneous bony regeneration is possible among patients presenting with tumor destruction of the skull base, precluding the need for neurosurgical intervention.