Radiation-induced lumbar plexopathy


Radiation-induced lumbar plexopathy or radiation-induced lumbosacral plexopathy is nerve damage in the pelvis and lower spine area occurring as a late side effect of external beam radiation therapy.
In general terms, such nerve damage may present in stages, earlier as demyelination and later as complications of chronic radiation fibrosis. RILP occurs as a result of radiation therapy administered to treat lymphoma or cancers within the abdomen or pelvic area such as cervical, ovarian, bladder, colon, kidney, pancreatic, prostate, testicular, colorectal, colon, rectal or anal cancer. The lumbosacral plexus area is radiosensitive and radiation plexopathy can occur after exposure to mean or maximum radiation levels of 50-60 Gray with a significant rate difference noted within that range.

Signs and symptoms

Lumbosacral plexopathy is characterized by any of the following symptoms; usually bi-lateral and symmetrical, though unilateral is known.
Symptoms are typically a step-wise progression with periods of stability in between, weakness often appearing years later. Weakness frequently presents in the lower leg muscle groups. Symptoms are usually irreversible.
Initial onset of symptoms may occur as early as 2 to 3 months after radiotherapy. The median onset is approximately 5 years, but can be highly variable, 2-3 decades after radiation therapy. One case study recorded the initial onset occurring 31 years post treatment.

Cause

The treatment's ionizing radiation is an activation mechanism for apoptosis within the targeted cancer, but it can also impact nearby healthy radiosensitive tissues, like the lumbosacral plexus. The occurrence and severity of RILP is related to the magnitude of ionizing radiation and the radiosensitivity of peripheral nerves may be further aggravated when combined with chemotherapy, like taxanes and platinum drugs, during treatment.

Pathophysiology

The pathophysiological process behind radiation's RILP nerve damage has been discussed and posited since the 1960s and still is without precise definition. Consensus exists on a progression of symptoms, with a stepping between initial inflammation and subsequent retractile fibrosis. Proposed mechanisms of nerve damage include microvascular damage supplying the myelin, radiation damage of the myelin, oxygen free radical cell damage, nerve compression neuropathy and a late fibro-atrophic poorly vascularised phase with retractile fibrosis.

Diagnosis

The more common source of lumbar plexopathy is a direct or secondary tumor involvement of the plexus with MRI being the typical confirmation tool. Tumors typically present with enhancement of nerve roots and T2-weighted hyperintensity. The differential consideration of RILP requires taking a medical history and neurologic examination.
RILP's neurological symptoms can mimic other nerve disorders. People may present with pure lower motor neuron syndrome, a symptom of amyotrophic lateral sclerosis. RILP may also be misdiagnosed as leptomeningeal metastasis often showing nodular MRI enhancement of the cauda equina nerve roots or having increased CSF protein content.
Other differential diagnoses to consider are Chronic Inflammatory Demyelinating Polyradiculoneuropathy, neoplastic lumbosacral plexopathy, paraneoplastic neuronopathy, diabetic lumbosacral plexopathy, degenerative disk disease, Osteoarthritis of the spine, Lumbar Spinal Stenosis, post-infectious plexopathy, carcinomatous meningitis, mononeuritis multiplex, and chemotherapy-induced plexopathy.
The testing to resolve a RILP diagnosis involves blood serum analysis, X-rays, EMG, MRI and Cerebrospinal Fluid analysis.

Prevention

Since RILP's neurological changes are typically irreversible and a curative strategy has yet to be defined, prevention is the best approach. Treating the primary cancer remains an obvious requirement, but lower levels of lumbar plexus radiation dosing will minimize or eliminate RILP.
One method to reduce the lumbosacral plexus' dosing is to include it with other at-risk organs that get spared from radiation.
Key to prevention is resolving the lack of clinical evidence between dosing the lumbar plexus and the late onset of neurological problems, a relationship confounded by low toxicity rates and the lack of an adequate population size, the lack of aggregate data pooling across multiple institutions.

Management

Treatment of RILP is primarily supportive with mental, physiological and social aspects and consideration of any aggravating neurological factors.
To prevent compounding existing RILP symptoms and to minimize further progression
The effect on the person with the condition, depends upon the type of impairment. Handicaps may include physical challenges, bowel and/or bladder dysfunction and may occur in multiple settings of work and home. Physical and occupational therapy are important elements in maintaining mobility and use of the lower extremities, along with assistive aides such as Ankle-Foot-Orthotics, cane, walkers, etc. Sensory reeducation techniques may be necessary for balance and lymphedema management may be required.
Pharmaceuticals that may be effective for RILP's neuropathic pain are
Non-pharmaceutical RILP considerations are
Functional impairment and residual pain can lead to social isolation. Cancer support groups are valuable resources to learn about the syndrome and therapeutic options, and are a means to voice emotions related to having cancer and surviving it.

Outcomes

With increasing cancer treatment survival rates, the quality of life for its survivors has become a public health priority. The effects of RILP can be debilitating. With no effective treatment to control radiation damage's progressive nature, limb dysfunction is the likely result.
Radiation damage's outcome is related to its initial onset time.
An exact occurrence rate has not been established. Literature on the topic is sparse. Clinical occurrences of RILP are rare, affecting between 0.3-1.3% of those treated with abdominal or pelvic radiation. The incidence rate is variable, dependent upon the irradiated zone, dosage level and method of delivery. For example when alternate dosing levels were compared, higher rates were observed, from 12 to 23%, the higher RILP rates occurring with higher dosages.

History

As of 1977 cases of lumbosacral neuropathy arising from radiation therapy had been rarely reported; one of the earliest cases was from 1948.
The incidence rate of peripheral neuropathy has been demonstrated to decrease when lower therapeutic radiation dosing levels are used. Radiation-induced Brachial Plexopathy may occur secondary to breast radiation therapy. Studies on RIBP have observed the brachial plexus' radiosensitivity. Injury was observed after dosages of 40 Gy in 20 fractions and RIBP significantly increased with doses greater than 2 Gy per fraction. RIBP is more common than lumbosacral radiculoplexopathy and has a clinical history with reduced dosing levels. RIBP occurrence rates were in the 60% range in the 1960s when 60 Gray treatments were applied in 5 Gray fractions; RIBP occurrences in the 2010s approach 1% with 50 Gray treatments applied in 3 Gy fractions.
RILP occurrence rates are estimated at 0.3% to 1.3%, though the actual rate is likely higher. The soft tissue damage leading to RILP is more commonly seen with exposure levels over 50 Gy, though has occurred with as little as 30 Gy. A major step toward reducing RILP occurrences is by limiting the lumbosacral plexus' dosing level when treating pelvic malignancies, limiting the mean dose to < 45 Gy. One approach to reduced levels, the plexus' mapping with other organs at risk, was clinically evaluated during the 2010s.
Clinical evidence of the cause-and-effect of prevention and the management of radiation induced polyneuropathy is limited.
In 2011 the National Radiation Oncology Registry was announced by the Radiation Oncology Institute. ROI and Massachusetts General Hospital would collect efficacy and side effect information from people who had undergone radiotherapy. In 2013 the American Society for Radiation Oncology joined the effort.

Research

Experimental approaches of RILP treatment include: