Guidelines on the Diagnosis and Management of Solitary Plasmacytoma of Bone (SBP) and Solitary Extramedullary Plasmacytoma (SEP)

3. Solitary Bone Plasmacytoma (SBP)

3.3. Treatment of SBP

3.3.1. Radiotherapy

This subject has recently been reviewed (Hu and Yahalom, 2000). Radical radiotherapy is the treatment of choice for solitary plasmacytoma of bone (SBP). In common with other rare tumours, the evidence base for treatment is largely composed of retrospective studies of small numbers of patients. Progression to multiple myeloma is common, despite high local control rates of 83-96% achieved with moderate doses of radiotherapy (Tsang et al, 2001; Mayr et al, 1990; Holland et al, 1992; Bolek et al, 1996; Liebross et al, 1998).

Data on dose response relationships is weak in most series, due to relatively low patient numbers and narrow range of doses used. Mendenhall et al, (1980) recommended a minimum dose of 40 Gy following a dose response analysis based on a review of the literature including 81 patients. They reported a 6% local failure rate in patients with SBP treated with doses of 40 Gy or above, in contrast to 31% for doses below 40 Gy. Some centres prefer to use higher doses of 45-50 Gy (Mayr et al, 1990; Liebross et al, 1998), but there is little evidence for a dose response curve above 40 Gy and sporadic local failures have been reported after doses of 50-60 Gy (Mayr et al, 1990, Liebross et al, 1998).

Tsang et al (2001) reported the Princess Margaret Hospital experience of 32 patients with SBP treated 1982-1993 and concluded that there was no convincing dose response relationship above 35 Gy. They reported that tumour bulk was the most significant factor influencing local control with 100% local control for SBP of 5cm or less and only 38% for SBP greater than 5cm. Their data suggests that bulky SBP of greater than 5cm requires a higher dose or perhaps combined modality treatment for effective local control. This finding is supported by several other authors (Mayr et al, 1990, Holland et al, 1992).

Based on the evidence above, a dose of 40 Gy in 20 fractions is recommended for SBP of 5cm or less. For SBP >5cm, a higher dose of up to 50 Gy in 25 fractions should be considered. An alternative strategy for tumours >5cm is preliminary chemotherapy followed by radiotherapy. This is theoretically attractive but there is little published evidence to support it.

The choice of clinical target volume for radiotherapy is also controversial. Some authors recommend that the entire involved bone is treated (Mayr et al, 1990). The rationale for this is largely based on marginal recurrences in retrospective series treated before modern imaging. MRI scanning accurately delineates bone, bone marrow and soft tissue extent of SBP for radiotherapy planning. Several recent series report excellent local control rates following irradiation of the tumour visualised on MRI scan with a margin, rather than the entire involved bone (Jyothirmayi et al, 1997; Liebross et al, 1998; Tsang et al, 2001).

The clinical target volume should include all tumour visible on MRI with a margin of at least 2cm. For small bones, such as vertebrae, this will include the entire involved bone, together with one uninvolved vertebra above and below. For larger bones, the clinical target volume will not necessarily include the entire bone, as this would involve unnecessary irradiation of normal tissues.

Assessment of response following radiotherapy depends upon changes in levels of monoclonal protein, resolution or progression of symptoms and evidence of new disease on imaging. Patients whose monoclonal protein disappears with treatment represent a category with a high likelihood of cure (see above) while many of those with persistent paraprotein after 1 year will develop MM. In contrast, post-treatment residual abnormalities on imaging are invariable, are difficult to assess and do not correlate with outcome (Liebross et al, 1998).

In 25-50% of patients the monoclonal protein disappears with radiotherapy. The monoclonal protein usually falls rapidly but the decline can be slow, lasting several years. Paraprotein persistence and level per se are not an indication for treatment but these patients should be monitored very carefully for signs of disease progression. Some patients revert to an apparently stable MGUS.

Patients not responding clinically to radiotherapy do not necessarily have residual tumour. They may have persistent symptoms and/or radiological changes due to existing bone destruction, while any residual paraprotein may reflect disease at other sites. In these circumstances a repeat biopsy is advisable to clarify the situation.

Recommendations:

3.3.2. Surgery

Radiotherapy remains the treatment of choice of the primary pathology and surgery is contra-indicated in the absence of structural instability or neurological compromise. However, early diagnosis and referral for a neurosurgical / orthopaedic opinion is advised in most cases with spinal involvement. Due to the development of modern spinal fixation systems over the last decade, surgical treatment is now a viable and successful option for patients who develop pain due to structural compromise within the vertebra, vertebral instability, neurological compromise or a combination of these. A number of case reports have been published recently supporting this rationale (Durr et al, 1997; Kawahara et al, 1998; Fang et al, 2001).

Loss of structural integrity requires some form of stabilization procedure and this is most frequently performed by posterior pedicle screw instrumentation. In cases of neurological compromise, decompression is also required. Anterior decompressive surgery usually allows best access to the pathology although some groups advocate a posterior approach to avoid the potential complications which can occur in trans-cavity access i.e. thoracotomy (Muhlbauer et al, 2000).

Due to the high chance of long-term survival in these patients (McLain and Weinstein, 1989), reconstruction of the destroyed anterior column of the spine may be required. Both biological (structural allografts) and mechanical (using expandable cages/spacers) reconstruction have been used. There are as yet no data to suggest the superiority of either, although from the theoretical point of view, the former seems more attractive.

The relatively new technique of vertebroplasty (Dudenay et al, 2002), which has been used with success in multiple myeloma, has not been reported in solitary plasmacytoma. It is contra-indicated in cases of neurological involvement. Treatment of vertebral collapse in solitary plasmacytoma with vertebroplasty is likely to be of limited value given that, in most cases, the degree of vertebral destruction renders the technique unsuitable.

The choice of surgery and approach needs to be tailored to the specific situation of each patient, depending on such variables as site and extent of tumour, general fitness and condition of the patient and the experience and preferences of the surgeon. Excellent results, in terms of neurological recovery and pain relief, have been reported in small series in the last decade using this rationale (Chataigner et al, 1998; Takahashi et al,1998).

It is often recommended that if surgery is required in the immediate or short term it should be carried out before radiotherapy is commenced. Surgery is more difficult in patients who have received radiotherapy. However, it is important to note that initial surgery may sometimes compromise radiotherapy, e.g. by the placing of metal supports, which may potentially shield areas of disease from effective radiation dose. Close liaison between haematologist, radiotherapist and surgeon is therefore crucial in planning optimum treatment for individual patients.

Recommendations:

3.3.3. Adjuvant chemotherapy

The role of adjuvant chemotherapy is at present not clearly defined (Hu and Yahalom, 2000; Abrams and Frassica, 2000). The addition of chemotherapy to radiotherapy in the treatment of SBP might be advantageous in improving local control and preventing or delaying progression to multiple myeloma. Some reports suggest that adjuvant chemotherapy may delay progression to multiple myeloma (Mayr et al, 1990; Holland et al, 1992). However, others observed no benefit (Shih et al, 1995; Tsang et al, 2001).

Only one small randomised controlled trial has been carried out. This suggested benefit from adjuvant melphalan and prednisolone, given for 3 years after radiotherapy (Aviles et al, 1996). After a median follow up of 8.9 years, 15 of 28 patients in the radiotherapy arm progressed to myeloma (54%) compared to only 3 of 25 patients (12%) in the combined modality treatment arm (p<0.01). Survival between the two groups of patients showed a significant survival advantage for combined modality therapy (p<0.01). Although this was a randomised controlled trial the number of patients was small. The results therefore need to be confirmed by further studies before concluding that adjuvant chemotherapy is beneficial, particularly in view of concerns about induction of myelodysplasia / secondary leukaemia and drug resistance.

Recommendations:

3.3.4. Bisphosphonates

Literature search revealed no publications dealing with the role of bisphosphonate therapy in the management of plasmacytoma. There are as yet no reported data on the role of bisphosphonates in preventing progression of stage I myeloma and MGUS. Such data might be able to be extrapolated to patients with plasmacytoma; however, currently an evidence-based recommendation cannot be made.

3.3.5. Thalidomide

Currently there is considerable interest in the role of thalidomide in plasma cell dyscrasias. Thalidomide has been successfully been used in the treatment of soft tissue plasmacytoma in the context of relapsed MM (Biagi et al, 2001) but there are currently no data on its effect in SBP.

3.3.6. Management of Apparent SBP with Positive MRI

Patients presenting as SBP but found on MRI scan to have more extensive disease (i.e. marrow involvement) should be considered as having MM. However if the plasmacytoma is the only cause of clinical symptoms and there is no other organ involvement it would be appropriate to treat the plasmacytoma according to the guidelines above and to defer chemotherapy until there are signs of progression, as per the UKMF/ BCSH guidelines for asymptomatic / indolent / smouldering myeloma (UK Myeloma Forum, 2001).