**6. Side effects**

Radiotherapy is generally well tolerated. The external beam localised fields' radiotherapy offers advantage of few acute and late toxicities. The potential side effects of radiotherapy are related to the fraction dose, total radiation dose, volume of the target, toxicities from other treatment approaches and the radiosensitivity of healthy surrounding tissues. The radiotherapy planning process uses established tolerance doses to avoid irreversible damage of critical organs, such as the lung, kidney, liver and spinal cord. Organ tolerances are based on the conventional radiotherapy (1.8–2 Gy per fraction daily, five times a week). When unconventional


**Table 4.** A summary of most common side effects of radiation treatment.

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 expectancy may not live long enough to experience such risks.

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

Radiotherapy is generally well tolerated. The external beam localised fields' radiotherapy offers advantage of few acute and late toxicities. The potential side effects of radiotherapy are related to the fraction dose, total radiation dose, volume of the target, toxicities from other treatment approaches and the radiosensitivity of healthy surrounding tissues. The radiotherapy planning process uses established tolerance doses to avoid irreversible damage of critical organs, such as the lung, kidney, liver and spinal cord. Organ tolerances are based on the conventional radiotherapy (1.8–2 Gy per fraction daily, five times a week). When unconventional

Skin Erythema, itching, dry desquamation, blister formation, hair loss in the treatment area

Mouth, oesophagus Xerostomia, sialitis, difficulty in swallowing, ulceration, trismus, osteoradionecrosis,

Small/large intestine Diarrhoea, cramping/colic, bowel movement, obstruction, bleeding, fistula, necrosis

Small/large intestine Loose stools/diarrhoea, cramps, bleeding, incontinence, rectal irritation

Bladder Bladder spasms, cystitis, urinary frequency, incontinence, haematuria

vertebroplasty, did not significantly impact outcomes of these procedures [58].

Clinical manifestation

Mouth, oesophagus Sore throat, dry mouth, trouble swallowing, taste loss

Skin Telangiectasia, atrophy, ulceration, pigmentation changes

Bladder Haematuria, epithelial atrophy, reduction in bladder capacity

Haematologic Neutropaenia, anaemia, thrombocytopaenia

**Table 4.** A summary of most common side effects of radiation treatment.

Systemic side effects Fatigue, anorexia, nausea/vomiting

fistula

**6. Side effects**

172 Update on Multiple Myeloma

**Acute side effects**

**Late side effects**

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

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 is accepted and acknowledged by medical communities [60].

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 is shown in **Table 4**.

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 in SF [30].

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.
