Skull Base Regeneration During Treatment With Chemoradiation for Nasopharyngeal Carcinoma: A Case Report
Background: Advanced cases of nasopharyngal carcinoma can present with skull base invasion. Treatment of these advanced cases with radiotherapy poses a challenge given proximity of tumor to critical neural structures as well as concern that a skull base defect and associated complications could develop with tumor regression.
Case Presentation: A 34-year-old male patient presented with a 7-cm nasopharyngeal tumor invading the skull base with destruction of the clivus and intracranial extension. He underwent a course of definitive chemoradiation, requiring use of adaptive radiotherapy, that resulted in complete tumor regression and is free of disease 5 years posttreatment. Imaging done during treatment demonstrated that significant regeneration of bone occurred simultaneously with tumor regression.
Conclusions: This case demonstrates that it is possible for bony regeneration to occur simultaneously with tumor regression in a patient with skull base invasion by tumor, precluding the need for neurosurgical intervention.
RT planning was complicated by the tumor’s contact with the brainstem and upper cervical SC, as well as proximity of the tumor to the optic apparatus. The patient underwent 2 replanning CT scans at 26 Gy and 44 Gy to evaluate for tumor shrinkage. These CT scans demonstrated shrinkage of the tumor away from critical neural structures, allowing the treatment volume to be reduced away from these structures in order to achieve required dose tolerances (brainstem < 54 Gy, optic nerves and chiasm < 50 Gy, SC < 45 Gy for this case). The replanning CT scan at 44 Gy, 5 weeks after treatment initiation, demonstrated that dramatic tumor shrinkage had occurred early in treatment, with separation of the remaining tumor from the area of the SC and brainstem with which it was initially in contact (Figure 1). This improvement allowed for shrinkage of the high-dose radiation field away from these critical neural structures.
Baseline destruction of the skull base by tumor raised concern for craniospinal instability with tumor response. The patient was evaluated by neurosurgery before the start of RT, and the recommendation was for reimaging during treatment and close follow-up of the patient’s symptoms to determine whether surgical fixation would be indicated during or after treatment. The patient underwent a replanning CT scan at 44 Gy, 5 weeks after treatment initiation, that demonstrated impressive bony regeneration occurring during chemoradiation. New bone formation was noted in the region of the clivus and bilateral occipital condyles, which had been absent on CT prior to treatment initiation. Another CT at 54 Gy demonstrated further ossification of the clivus and bilateral occipital condyles, and bony regeneration occurring rapidly during chemoradiation. The posttreatment CT 3 months after completion of chemoradiation demonstrated complete skull base regeneration, maintaining stability of this area and precluding the need for neurosurgical intervention (Figure 2).
During RT,
The patient had no evidence of disease at 5 years posttreatment. After completing treatment, the patient experienced ongoing intermittent nasal congestion and occasional aural fullness. He experienced an early decay of several teeth starting 1 year after completion of RT, and he continues to visit his dentist for management. He experienced no other treatment-related toxicities. In particular, he has exhibited no signs of neurologic toxicity to date.
Discussion
RT for NPC is complicated by the proximity of these tumors to critical surrounding neural structures. It is challenging to achieve the required dose constraints to surrounding neural tissues while delivering the usual 70-Gy dose to the gross tumor, especially when the tumor comes into direct contact with these structures.
This case provides an example of response-adapted RT using imaging during treatment to shrink the high-dose target as the tumor shrinks away from critical surrounding structures.7 This strategy permits delivery of the maximum dose to the tumor while minimizing radiation dose, and therefore risk of toxicity, to normal surrounding structures. While it is typical to deliver 70 Gy to the full extent of tumor involvement for H&N tumors, this was not possible in this case as the tumor was in contact with the brainstem and upper cervical SC. Delivering the full 70 Gy to these areas of tumor would have placed this patient at substantial risk of brainstem and/or SC toxicity. This report demonstrates that response-adapted RT with shrinking fields can allow for tumor control while avoiding toxicity to critical neural structures for cases of locally advanced NPC in which tumor is abutting these structures.
Bony regeneration of the skull base following RT has been reported in the literature, but in limited reviews. Early reports used plain radiography to follow changes. Unger and colleagues demonstrated the regeneration of bone using skull radiographs 4 to 6 months after completion of RT for NPC.8 More recent literature details the ability of bone to regenerate after RT based on CT findings. Fang and colleagues reported on 90 cases of NPC with skull base destruction, with 63% having bony regeneration on posttreatment CT.9 Most of the patients in Fang’s report had bony regeneration within 1 year of treatment, and in general, bony regeneration became more evident on imaging with longer follow-up. Of note, local control was significantly greater in patients with regeneration vs persistent destruction (77% vs 21%, P < .001). On multivariate analysis, complete tumor response was significantly associated with bony regeneration; other factors such as age, sex, radiation dose, and chemotherapy were not significantly associated with the likelihood of bony regeneration.
Our report details a nasopharyngeal tumor that destroyed the skull base with no intact bony barrier. In such cases, concern arises regarding craniospinal instability with tumor regression if there is not simultaneous bone regeneration. Tumor invasion of the skull base and C1-2 vertebral bodies and complications from treatment of such tumor extent can lead to symptoms of craniospinal instability, including pain, difficulty with neck range of motion, and loss of strength and sensation in the upper and lower extremities.10 A case report of a woman treated with chemoradiation for a plasmacytoma of the skull base detailed her posttreatment presentation with quadriparesis resulting from craniospinal instability after tumor regression.11 Such instability is generally treated surgically, and during this woman’s surgery, there was an injury to the right vertebral artery, although this did not cause any additional neurologic deficits.
