**5. Surgery and radiation treatment**

deficiency, sensory symptoms and bowel and bladder dysfunction [48]. Immediate diagnosis and treatment are very important in the preservation of neurological function in patients with spinal cord compression. Pain control, relief of spinal cord compression and improvement of neurologic function are the main goals of treatment. High-dose steroids must soon be initiated upon spinal cord compression diagnosed to obtain an antineoplastic and an antioedema effect [49]. In patients with neurologic symptoms directly due to cord compression, radiation therapy is given along with dexamethasone, and up to half of patients may have improvement of motor function [50]. In the largest retrospective studies, radiotherapy alone improves motor function in 75% of patients with spinal cord compression due to MM. A 1-year local

**Table 3.** A summary of published data on palliative radiotherapy recalcification response in the treatment of patients

Radiation treatment can be used as fractionated external beam radiotherapy (EBRT) or stereotactic body RT (SBRT). Both methods are effective for palliative treatment and local tumour control. SBRT is a non-invasive treatment option for spinal disease in the absence of a high-grade spinal cord compression. SBRT allows the treatment of small- or moderate-sized tumours, even in close proximity to the spinal cord, in either a single or a limited number of dose fractions [48]. SBRT with a single 24 Gy fraction gives excellent tumour control [48].

Since myeloma is a very radiosensitive tumour, EBRT is an appropriate approach for patients who are not considered surgical treatment and it is also indicated after decompression intervention. There was no randomised trial that compared radiotherapy alone to radiotherapy plus upfront neurosurgery. Thus, radiotherapy alone is considered the standard treatment of

control was 100% and a 1-year survival was 94% [51].

**Clinical study Number** 

170 Update on Multiple Myeloma

Rudzianskiene et al.

[44]

with MM.

**of patients** **Number of irradiated sites**

101 101 8 Gy vs.

**Total dose (Gy)**

Balducci et al. [7] 52 52 16–50 50 The influence of total radiation

30 Gy

Mose et al. [12] 42 71 18–45 46.4 There was no significance difference

Stolting et al. [5] 138 272 2–60 44.7 There was no significance difference

**Overall response (%)**

35.9 vs. 32.1

**Comments**

recalcification.

recalcification.

between recalcification response and higher radiation dose, usage of bisphosphonates, concurrent chemotherapy increase response of

dose, concurrent chemotherapy and bisphosphonates was not evaluated.

There was no significant difference between recalcification response and higher radiation dose, usage of bisphosphonates and there was no influence of concurrent chemotherapy.

between recalcification response and total radiation dose, concurrent chemotherapy and bisphosphonates increase response of

> Surgical management of MM-related bone lesions sometimes is carried out due to disease sensitivity of radiation treatment and chemotherapy. The most common indications for surgical procedures are unstable fractures and spinal cord compression when bone fragments

protrude from a vertebral fracture [49]. Vertebroplasty and kyphoplasty are carried out by fibroscopic percutaneous injection of polymethylmethacrylate into the fractured vertebrae in order to relieve pain. These procedures should be considered for symptomatic vertebral compression fractures, and this is a procedure of choice to improve the quality of life [3]. Vertebroplasty combined with post-operative radiotherapy is an effective approach in the pain palliation, maintaining the stability of vertebral column and improving the quality of life of patients. Some randomised clinical studies demonstrated that surgery and post-operative radiotherapy are more effective in the treatment of vertebral fractures than radiotherapy alone [56, 57]. Treating these patients with radiotherapy before surgery procedure allows for tumour shrinkage and can enable these patients to become candidates for vertebroplasty [58]. The study performed by Hirsch et al. reported that the timing of radiotherapy, before or after vertebroplasty, did not significantly impact outcomes of these procedures [58].

fractionation regimens are introduced, the total radiation dose must be adjusted to avoid high risk of side effects, as lower total doses limit acute toxicity. In general, palliative radiotherapy doses are delivered with a larger dose per fraction. These hypofractionated regimens may provide the benefit of earlier response but with a greater risk of late side effects [59]. Late side effects occur from months to years after radiation treatment, and patients with a short life

The Role of Radiology and Radiotherapy for Multiple Myeloma

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173

Side effects of radiation are generally mild, limited to the radiotherapy site and can be predicted. Most acute side effects arising within 90 days are self-limited, lasting days to weeks and resolve within few weeks with supportive care. Acute toxicities as fatigue, nausea/vomiting, mucositis, oesophagitis and bowel irritation are often easily managed and reversible. The more critical side effects are late side effects, emergent from cellular and vascular atrophy, and lead to the reduction of normal tissue function and organ dysfunction, which may

In 1982, the Radiation Therapy Oncology Group (RTOG) developed the Radiation Morbidity Scoring Criteria to classify radiotherapy effects. RTOG score has been widely employed and

Skin reactions are usually nominal during radiation treatment for bone metastases and are treated similar to burns. Patients treated with large volumes including pelvis, epigastrium or thoracolumbar spine region may experience nausea and/or vomiting. Prophylactic antiemetics can be administered 30–60 min prior to radiotherapy and continued on as needed. Hematologic side effects are mild and transient, but bone marrow suppression may occur if the patients are receiving treatment to large targets, when the total radiation dose is moderate or high, and a significant proportion of marrow is included, especially in heavily pretreated patients. Mucositis and oesophagitis causing difficult and painful swallowing occur after treatment to the head and neck or thorax. It should be treated with dietary modifications, oral rinses, antifungals, analgesics and cytoprotective agents. Radiation enteritis manifested by cramping; frequent, loose stools and occasionally bleeding may occur if large amounts of small intestine are included. Treating the pelvis may also result in short-lived diarrhoea [61]. A summary of clinical manifestations of the most common side effects of radiation treatment

No significant differences were observed between SF and MF radiotherapy for bone metastases of solid tumours in the systematic review performed by Chow et al. [30]. Only two studies reported more acute toxicities (characterised as grades 2–4) in the group of MF regimens than

Based on the analysis of medical literature, the side effects of radiotherapy in multiple myeloma patients were generally mild. Balducci et al. [7] identified 44% of patients (n = 23) with side effects (grades 1–2): haematological toxicity in 48%, gastroenteric toxicity in 26%, pharyngeal toxicity in 9% and cutaneous toxicity in 17% patients. Mose et al. [12] reported about 54% side effects mostly of grades 1–2; grade 3 in 4% (haematological side effects, mucositis, creatinine level). These data correspond with Matuschek et al. [62] as this study reported 37% side effects with 50% grade 1 and 47.2% grade 2 and one patient grade 3 dysphagia.

expectancy may not live long enough to experience such risks.

develop months to years later, but they are very rare.

is shown in **Table 4**.

in SF [30].

is accepted and acknowledged by medical communities [60].
