Intensity-modulated radiation therapy administered to a previously irradiated spine is effective and well-tolerated

Purpose This study sought to discern the clinical outcomes of intensity-modulated radiation therapy (IMRT) administered to the spine in patients who had undergone previous radiotherapy. Methods A total of 81 sites of 74 patients who underwent previous radiotherapy administered to the spine or peri-spine and subsequently received IMRT for the spine were analyzed in this study. The prescribed dose of 80 Gy in a biologically effective dose (BED) of α/β = 10 (BED10) was set as the planning target volume. The constraint for the spinal cord and cauda equine was D0.1 cc ≤ 100 Gy and ≤ 150 Gy of BED for re-irradiation alone and the total irradiation dose, respectively. Results The median follow-up period was 10.1 (0.9–92.1) months after re-irradiation, while the median interval from the last day of the previous radiotherapy to the time of re-irradiation was 15.6 (0.4–210.1) months. Separately, the median prescript dose of re-irradiation was 78.0 (28.0–104.9) of BED10. The median survival time in this study was 13.9 months, with 1-, 3-, and 5-year overall survival rates of 53.7%, 29.3%, and 26.6%, respectively. The 1-, 3-, and 5-year local control rates were 90.8%, 84.0%, and 84.0%, respectively. Neurotoxicity was observed in two of 72 treatments (2.8%) assessed after re-irradiation. Conclusion Re-irradiation for the spine using IMRT seems well-tolerated. Definitive re-irradiation can be a feasible treatment option in patients with the potential for a good prognosis (AU)

Intensity-modulated radiation therapy administered to a previously irradiated spine is effective and well-tolerated.

PURPOSE: This study sought to discern the clinical outcomes of intensity-modulated radiation therapy (IMRT) administered to the spine in patients who had undergone previous radiotherapy. METHODS: A total of 81 sites of 74 patients who underwent previous radiotherapy administered to the spine or peri-spine and subsequently received IMRT for the spine were analyzed in this study. The prescribed dose of 80 Gy in a biologically effective dose (BED) of α/ß = 10 (BED10) was set as the planning target volume. The constraint for the spinal cord and cauda equine was D0.1 cc ≤ 100 Gy and ≤ 150 Gy of BED for re-irradiation alone and the total irradiation dose, respectively. RESULTS: The median follow-up period was 10.1 (0.9-92.1) months after re-irradiation, while the median interval from the last day of the previous radiotherapy to the time of re-irradiation was 15.6 (0.4-210.1) months. Separately, the median prescript dose of re-irradiation was 78.0 (28.0-104.9) of BED10. The median survival time in this study was 13.9 months, with 1-, 3-, and 5-year overall survival rates of 53.7%, 29.3%, and 26.6%, respectively. The 1-, 3-, and 5-year local control rates were 90.8%, 84.0%, and 84.0%, respectively. Neurotoxicity was observed in two of 72 treatments (2.8%) assessed after re-irradiation. CONCLUSION: Re-irradiation for the spine using IMRT seems well-tolerated. Definitive re-irradiation can be a feasible treatment option in patients with the potential for a good prognosis.

Radiation-induced intradural malignant peripheral nerve sheath tumor of the cauda equina with diffuse leptomeningeal metastasis.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare, affecting only a small portion of the general population. In many cases, MPNSTs occur in association with neurofibromatosis Type 1 and at times arise secondary to previous radiation therapy (RT). These tumors can be found essentially anywhere a peripheral nerve is present, but they rarely originate primarily from the spinal nerve or cauda equina and cause leptomeningeal spread. This report describes the treatment course of a 43-year-old man with a history of testicular seminoma treated with RT a decade before, who was found to have a large sacral MPNST. The patient underwent complete sacrectomy for gross-total resection. Despite this effort, he was eventually found to have metastatic lesions throughout the spine and brain, ultimately resulting in acute hydrocephalus and death. Biopsy results of these metastatic lesions proved to be characteristic of his original MPNST. The literature is also reviewed and the diagnostic modalities, management strategies, and prognosis of MPNST are discussed.

Postradiation lower motor neuron syndrome: case series and literature review.

A variety of neurological syndromes has been described after irradiation of the distal spinal cord and cauda equina, mainly as treatment for testicular cancer and lymphoma. One of these syndromes is a rare lower motor neuron syndrome, manifested by flaccid paraparesis. Medical files of patients with postradiation lower motor neuron syndrome treated in our neuromuscular clinic from 2005 to 2012 were reviewed. The diagnosis was based on past irradiation of the distal spinal cord and cauda equina, slowly progressive lower limb weakness, characteristic electrophysiological studies, and no alternative diagnosis. In addition, a systematic review of the literature on similar cases was performed using PUBMED. We identified five patients with postradiation lower motor neuron syndrome in our clinic charts. Three of them were irradiated due to seminoma, and the other two due to lymphoma. 45 additional similar cases were found in a literature search, mainly male (89 %), with testicular cancer (67 %), irradiated at mean age of 33 years, with an average irradiation dose of 5,225 cGy (range 3,000-14,600), and a latency period between irradiation and symptoms onset ranging from 3 months to 27 years (average 9 years). Magnetic resonance imaging was done only in few, showing gadolinium enhancement of the cauda equina in close to half of them (7/16). Our patients and those previously described in the literature form a distinct clinical and electrophysiological syndrome that might be more frequent then previously expected, and should be not overlooked.

Prominent cauda equina involvement in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

In chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), it has not been well known which segment of the peripheral nerves, distal or proximal, is more often involved in electrophysiological examination. This study compares nerve conductions at proximal segments with those at distal segments in 11 patients with CIDP. To obtain cauda euqina conduciton time (CECT), compound muscle action potentials (CMAPs) were elicited by magnetic stimulation using a MATS coil from the abductor hallucis muscle. CECT was prolonged in 9 patients (81.8%), whereas the ankle-knee conduction was delayed in 4 (36.4%). The proximal segments are more frequently involved than the distal segments in this disorder.

Neurophysiological and histopathological evaluation of low-dose radiation on the cauda equina and postlaminotomy fibrosis: an experimental study in the rat.

STUDY DESIGN: We evaluated the electrophysiological changes to the cauda equina after low-dose external irradiation in a postlaminotomy fibrosis model in rats. OBJECTIVE: To clarify the immediate and long-term electrophysiological responses of antifibrotic radiation therapy in a fibrosis model. SUMMARY OF BACKGROUND DATA: Low-dose perioperative radiation therapy inhibits scar formation. However, its efficacy for preventing fibrosis-induced compressive neuropathy and its potential adverse effect on underlying neural structures have not been studied. METHODS: Twenty-four rats were placed in 3 groups of 8: group I, sham operation (laminar exposure alone) with a single fraction of 700 cGy external irradiation given using a 9-MeV electron beam 24 hours postsurgery; group II, left L5 hemilaminectomy (laminotomy) alone; and group III, left L5 hemilaminectomy with the same radiation protocol as group 1. We recorded mixed-nerve-elicited somatosensory-evoked potentials (M-SSEP)- and dermal (D)-SSEP at the thoracolumbar junction, and L1-L2 interspinous ligament after percutaneously stimulating the posterior tibial nerve at the bilateral medial ankle and L5 dermatomal fields. We compared the potentials recorded immediately before, 30 minutes, 2 weeks, and 1, 2, and 3 months after surgery on the operated and nonoperated sides. We used gross dissection and histologic sections to evaluate the degree of perineural fibrosis and walking-track analysis for neurologic evaluation. RESULTS: Pre- and postoperative (30 minutes and 2 weeks) M- and D-SSEP were not statistically different. In group II, the relative amplitude of D-SSEP (elicited from 5 dermatomes) 1, 2, and 3 months postsurgery was lower; however, the M-SSEP in all groups and D-SSEP of groups I and III remained constant. Histologic evaluation of radiation efficacy showed that the frequency and extent of peridural fibrosis was consistently lower in group II than in group III. CONCLUSION: Low-dose irradiation reduced peridural fibrosis and prevented fibrosis-induced radiculopathy. The radiation caused no adverse neuropathic complications.

Cauda equina tolerance to high-dose fractionated irradiation.

PURPOSE: To report late neurologic toxicity rates and clinical outcomes for patients treated with high dose fractionated radiation therapy using three-dimensional treatment planning and combined proton and photon beams to portions of the cauda equina (L2-coccyx). METHODS AND MATERIALS: Medical records of 53 patients treated to fields encompassing the cauda equina were reviewed for the onset of neurologic symptoms in the absence of local failure. All doses were normalized to equivalent dose delivered in 2-Gy fractions. Median cauda dose was 65.8 cobalt Gray equivalents (CGE) (range, 31.9-85.1). Median follow-up was 87 months (range, 14-217 months). RESULTS: Nineteen patients experienced local recurrences, and 13 others had neurologic toxicity. A total of 54% (i.e., 7/13) of the toxicities occurred 5 years or more after treatment. Median caudal dose was 73.7 CGE in the group with neurologic toxicity, and 55.6 CGE in those without. On multivariate actuarial analysis, cauda dose and gender were statistically significant for neurotoxicity at p = 0.002 and p = 0.017, respectively. The estimated tolerance doses 5 years from treatment, TD 5/5 and TD 50/5, were 55 CGE and 72 CGE, respectively, for males and 67 CGE and 84 CGE for females. The tolerance doses were about 8 CGE lower when estimated at 10 years from treatment. Disease-free survival rates at 5 and 10 years were 66% and 53%, respectively. CONCLUSIONS: This study suggests that the probability of neurotoxicity is a relatively steep function of dose to cauda equina (slope gamma50 = approximately 3). The cauda equina tolerance is greater for females than males by about 11 CGE (at 2 CGE per fraction). Extended follow-up is necessary to accurately assess neurologic damage and then differentiate that phenomenon from local recurrence; the traditional 5-year assessment has limited meaning in this population. Local control remains an issue for these patients, even with the radical doses used.

Donut-shaped high-dose configuration for proton beam radiation therapy.

BACKGROUND: The authors report on the conception and first clinical application of a donut-shaped high-dose configuration for proton therapy (PT). This approach allows one to intensify target volume dose coverage for targets encompassing a critical, dose-limiting structure--like here, the cauda equina--, whilst delivering minimal dose to other healthy structures surrounding the target, thereby reducing the integral dose. METHODS AND RESULTS: Intensity-modulated PT methods (IMPT) for spot scanning were applied to create and deliver a donut-shaped high-dose configuration with protons, allowing treating > 75% of the target with at least 95% of the prescribed dose of 72.8 CGE, whilst restricting dose to the cauda equina to 60-65 CGE. Integral dose was lower by a factor of 3.3 as compared to intensity-modulated radiotherapy with photons (IMXT). CONCLUSION: IMPT and spot scanning technology allow a potentially clinically useful approach which is also applicable to spare other critical structures passing through a target volume, including spinal cord, optic nerves, chiasm, brain stem, or urethra.

Radiotherapy-induced malignant peripheral nerve sheath tumor of the cauda equina.

STUDY DESIGN: Case report. OBJECTIVES: To report a rare case of radiation-induced malignant peripheral nerve sheath tumor of the cauda equina 10 years after treatment for testicular seminoma. SUMMARY OF BACKGROUND DATA: Development of malignant peripheral nerve sheath tumor after irradiation is well recognized and often associated with a dismal prognosis. There have been isolated reports of malignant peripheral nerve sheath tumor developing in sites of previous irradiation for testicular seminoma. METHODS: Retrospective review of case records and imaging. RESULTS: A 38-year-old man presented with signs of cauda equina syndrome. Ten years previously, he had undergone right radical inguinal orchidectomy and adjuvant para-aortic radiotherapy as treatment for Stage I testicular seminoma. Magnetic resonance imaging demonstrated an inoperable intra- and extradural tumor leading to significant cauda equina compression. CT-guided biopsy revealed a diagnosis of malignant peripheral nerve sheath tumor, most likely due to previous radiotherapy. His clinical condition did not improve, and he underwent a course of palliative chemotherapy. CONCLUSIONS: Postirradiation malignant peripheral nerve sheath tumors are rare and occur in a population at high risk of developing second malignancies. The authors report the fourth case resulting from adjuvant radiotherapy for testicular seminoma, with the present report being the first report of extensive intradural tumor leading to cauda equina syndrome.

Plexiform neurofibroma of the cauda equina. Case report.

Plexiform neurofibroma of the cauda equina has been reported only twice previously. The authors report the first pediatric patient in whom such a tumor has been found. A 4-year-old boy presented with low-back pain that radiated bilaterally into the L-4 and L-5 dermatomes. A dermal sinus noted at the midthoracic level was surrounded by a hemangiomatous lesion. Magnetic resonance imaging confirmed the presence of the dermal sinus and revealed a well-defined lumbosacral mass that showed heterogeneous intensity with irregular enhancement. Intraoperatively, a solid mass, which engulfed the entire cauda equina, could not be dissected from the roots. The dermal sinus tract, however, was excised from the thoracic spine. The patient underwent radiotherapy to control the tumor and relieve his pain. Plexiform neurofibromas of the cauda equina are characterized by an insidious and progressive clinical course. The tumor mass may engulf all the roots of the cauda equina. No plexiform neurofibroma of the cauda equina has been reported to be associated with neurofibromatosis Type 1. The authors assume that the thoracic-level dermal sinus observed in this child was an incidental finding.

[Radiogenic amyotrophy. Cauda equina lesion as a late radiation sequela]. / Radiogene Amyotrophie. Cauda-equina-Läsion als Strahlenspätfolge.

PURPOSE: Course and pathophysiology of a typical syndrome after irradiation of the cauda equina were studied. PATIENTS AND MATERIALS: 7 patients with irradiation damage of the cauda equina were examined clinically and neurophysiologically. RESULTS: After a mean delay of 5 years and 6 months all patients developed an ascending lower motor neuron weakness of the legs without pain, in part accompanied with mild sensory and sphincter symptoms. Electromyography, evoked potentials and neurography were important for the differential diagnosis to tumor infiltration. The course was progredient. DISCUSSION: For a long time, the underlaying damage was thought to be in the anterior horn cell body. The course of the studied patients with additional sensory and vegetative symptoms implies for a direct bilateral damage of the cauda equina. A better term for the syndrome is "post-irradiation cauda-equina-syndrome".

The post-irradiation lower motor neuron syndrome neuronopathy or radiculopathy?

It is not known whether the post-irradiation lower motor neuron syndrome results from radiation damage to motor neuron cell bodies or from damage to the nerve roots of the cauda equina. We studied six cases who had presented with testicular neoplasms, subsequently undergoing irradiation that encompassed inter alia para-aortic nodes with co-irradiation of the distal spinal cord and cauda equina. A predominantly motor disorder affecting the legs ensued after variable and often prolonged latencies (3-25 years). However, all patients also developed mild sensory features either initially or on prolonged follow-up. Sural sensory nerve action potentials (SNAPs) were normal in five. Mild sphincter symptoms occurred in three of five surviving cases after a mean of 7.9 years. MRI showed gadolinium enhancement of the cauda equina in two of three patients. The first reported neuropathological study, uncomplicated by metastatic disease, of the conus and cauda equina was performed in one patient who died. This showed a radiation-induced vasculopathy of the proximal spinal roots, with preservation of motor neuronal cell bodies and spinal cord architecture. These clinical, radiological, neurophysiological and pathological findings all point to a predominantly, but not exclusively, motor radiculopathy affecting the irradiated portion of the cauda equina proximal to the dorsal root ganglia. Radiation exposure exceeded 40 Gy both in our series and in previous reports. The natural history of this disorder is one of relentless deterioration occasionally punctuated by 1-2-year periods of stability. Post-irradiation lumbosacral radiculopathy is a more accurate name for this condition.

Cauda equina paraganglioma with subsequent intracranial and intraspinal metastases.

A case of cauda equina paraganglioma is described; subsequent intracranial and intraspinal metastases occurred after partial resection and adjunctive radiotherapy. Cerebrospinal fluid dissemination is a rare complication of spinal paragangliomas. Factors predictive of this unusual biological behaviour are discussed.

Neurological observations after local irradiation and hyperthermia of rat lumbosacral spinal cord.

PURPOSE: Investigation of the effects of hyperthermia on the radiation response of rat lumbosacral spinal cord with respect to: (a) incidence of paralysis, (b) latency, (c) histopathology, and (d) tumor induction. METHODS AND MATERIALS: Rat lumbosacral spinal cord with the cauda equina was single-dose irradiated with 15 to 32 Gy of x-rays. Hyperthermia for 30 min at a spinal cord temperature of 41.1, 42.3, and 42.6 +/- 0.4 degrees C was applied 5 to 10 min after irradiation by means of a 434 MHz microwave applicator. Animals were observed for 21 months while recording myelopathy and development of tumors. RESULTS: The latent period for hind leg paralysis decreased with increasing radiation dose from 359 +/- 31 days (n = 9) after 20 Gy to 200 +/- 4 days (n = 5) after 32 Gy. Hyperthermia enhanced the radiation response of the lumbosacral spinal cord as evidenced by shortening of the latent period for paralysis and a decrease in the biological effective dose. After 20 Gy followed by 30 min 41.1 degrees C, latency was diminished to 214 +/- 16 days (n = 7, p < 0.001 vs. 20 Gy alone). The ED50 was 21.1 Gy, which was diminished to values between 16 and 17 Gy if radiation was followed by hyperthermia, giving a thermal enhancement ratio between 1.24 and 1.32. Histopathological examination of the spinal cord after combined treatment of x-rays and hyperthermia showed necrosis of nerve roots. Irradiation with 16, 20, 24, and 28 Gy (n = 77) alone led to tumor induction in 17 +/- 8% of the animals (pooled data). If followed by hyperthermia (n = 96), it was increased to 33 +/- 12% (p < 0.01). Most tumors induced by radiation and hyperthermia were sarcomas. CONCLUSION: First, the radiation response of rat lumbosacral spinal cord was enhanced by heat. Second, latency for paralysis was shortened in the lower dose range. Third, no difference in pathology between x-rays alone or in combination with hyperthermia. Fourth, hyperthermia did increase radiation carcinogenesis.

Ependymomas of the filum terminale in childhood: report of four cases and review of the literature.

Four cases of ependymoma of the filum terminale occurring in childhood are reported. The clinical, therapeutic and prognostic features seen at this age and in adults were compared.

Ependymoma of the filum terminale: treatment and prognostic factors in a series of 28 cases.

A series of 28 ependymomas arising in the filum terminale was divided into two groups based on the presence/absence of connections with the conus medullaris and/or roots of the cauda equina. Group A comprised ependymomas having no connections with the contiguous structures and group B those either infiltrating or adhering to such structures. Factors having a positive influence on the prognosis (risk of recurrence) were: 1) clinical history under one year (p < 0.01); 2) confinement of tumour to the filum terminale (p < 0.01); 3) total tumour removal (p < 0.05). Postoperative radiotherapy had no appreciable effect on outcome. The combination of significant factors was in turn significantly influenced by the mode of tumour growth, which proved to be the cardinal factor in prognosis. This point is examined in the light of the published work.

Treatment outcome and complications in patients treated for malignant epidural spinal cord compression (SCC).

Sixty-seven episodes of spinal cord compression (SCC) were retrospectively evaluated regarding presenting features and treatment outcome. They were divided into three motor function groups. Group 1 consisted of 35 ambulatory patients, group 2 of 29 non-ambulatory patients and group 3 of three paraplegic patients. Lower extremity weakness was usually a late presenting feature and was frequently rapidly progressive. We suggest that SCC is an emergency, as successful treatment is unlikely if motor function is poor. All of the group 1 patients completing treatment remained ambulatory, in contrast to group 2 patients, in which only 25% regained the ability to walk, and group 3 patients, none of whom regained the ability to walk. Initial surgery or initial radiotherapy appeared to be equally effective in restoring or maintaining the ability to walk. Survival of patients ambulatory at completion of treatment was superior to that of non-ambulatory patients (p less than 0.03). Analysis of steroid-related complications suggested that frequent, severe and sometimes fatal complications can result from prolonged use with these drugs.

Radiation-induced nerve root degeneration and hypertrophic neuropathy in the lumbosacral spinal cord of rats: the relation with changes in aging rats.

Three-month-old WAG/Rij rats were irradiated with 300 kV X-rays on the lumbar region of the spinal column with doses below the level for causing paralysis due to radiation radiculomyelopathy. 8--9 months after irradiation, degeneration of predominantly the ventral nerve roots of the cauda equina was boserved. Three stages were distinguishable: I) Demyelination and proliferation of Schwann cells; II) Local swelling of ventral nerve roots, with concentric layers of Schwann cells resembling hypertrophic neuropathy; III) Malignant Schwannoma, invading roots and spinal cord. It is concluded that the degenerative and proliferative lesions represent a continuous series of stages of slowly progressive lesions. The ventral nerve root degeneration (1st stage) is similar to that observed in aging, unirradiated rats, normally developing at the age of 18--20 months.