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The Role of Radiation in Multiple Myeloma or Plasmacytoma.

See the NCCN guidelines for radiation for local plasmacytomas and for bone disease.

If the tumor is localized (like a plasmacytoma) then high dose (50Gy) radiation may control it. In the studies below, local control of an isolated plasmacytoma occurred in 88 - 95%. The cure rate is good for isolated plasmacytomas that are not in the bone. Those that start in the bone will frequently develop other bone lesions and full fledged multiple myeloma.

If the disease is widespread at the time of diagnosis  multiple myeloma) then low dose radiation (10 - 20Gy) will often relive local bone pain and prevent bone fractures. The palliative response rate for radiation to the bone or soft tissue runs between 75% to 97%  as  noted below.


Some of the studies are noted below:

Palliative radiotherapy in plasma cell myeloma.

Adamietz IA, Radiother Oncol 1991 Feb;20(2):111-6 Department of Radiotherapy, Medical School, Hannover, F.R.G.

Pain symptoms caused by bone lesions of multiple myeloma can be relieved by a local irradiation treatment. To estimate the influence of systemic treatment on the palliative effect of local radiotherapy the records of 70 myeloma patients treated with chemotherapy combined with or followed by local irradiation were reviewed. The local response rate, defined as complete pain relief at the irradiated site, was 80% in patients receiving irradiation during chemotherapy (melphalan and prednisone) and this palliative effect endured 31.8 +/- 3.6 months. If irradiation was started in the period without systemic treatment the local response rate was 39.6% and lasted 24.8 +/- 17.9 months. In sites treated with more than one radiotherapy course 94% response rate after the first treatment, 56% after the second treatment and no response after the third course was achieved.  It is concluded that irradiation during concomitant chemotherapy is superior to radiotherapy performed in a period without systemic treatment. Local long-term palliation can only be achieved by a sufficient high radiation dose.

Radiation therapy for the palliation of multiple myeloma.

Leigh BR,  Int J Radiat Oncol Biol Phys 1993 Apr 2;25(5):801-4 Department of Radiation Oncology, University of Arizona College of Medicine and Cancer Center, Tucson 85724.

PURPOSE: This reviews the experience at the University of Arizona in an effort to define the minimum effective radiation dose for durable pain relief in the majority of patients with symptomatic multiple myeloma. METHODS AND MATERIALS: The records of 101 patients with multiple myeloma irradiated for palliation at the University of Arizona between 1975 and 1990 were reviewed. Three hundred sixteen sites were treated. Ten sites were asymptomatic, including six hemibody fields with advanced disease unresponsive to chemotherapy and four local fields with impending pathological fractures. Three hundred six evaluable symptomatic sites remained. The most common symptom was bone pain. Other symptoms included neurological impairment and a palpable mass. RESULTS: Total tumor dose ranged from 3.0 to 60 Gy, with a mean of 25 Gy. Symptom relief was obtained in 297 of 306 evaluable symptomatic sites (97%). Complete relief of symptoms was obtained in 26% and partial relief in 71%. Symptom relief was obtained in 92% of sites receiving a total dose less than 10 Gy (n = 13) and 98% of sites receiving 10 Gy or more (n = 293). No dose-response could be demonstrated. The likelihood of symptom relief was not influenced by the location of the lesion or the use of concurrent chemotherapy. Of the 297 responding sites, 6% (n = 19) relapsed after a median symptom-free interval of 16 months. Neither the probability of relapse nor the time to relapse was related to the radiation dose. Retreatment of relapsing sites provided effective palliation in all cases. CONCLUSION: Radiation therapy is effective in palliating local symptoms in multiple myeloma. A total dose of 10 Gy should provide durable symptom relief in the majority of patients.

Palliative radiation therapy for multiple myeloma

Minowa Y, Nippon Igaku Hoshasen Gakkai Zasshi 1996 Dec;56(14):1056-60

Department of Radiology, Faculty of Medicine, Kyoto University.

PURPOSE: Radiation therapy is a useful palliative modality for refractory lesions of multiple myeloma. It has been reported that total doses of 10 to 20 Gy are usually adequate to obtain some degree of pain relief. However, there are many patients who need additional doses to obtain sufficient pain relief. In this study, we retrospectively analyzed the records of patients with multiple myeloma irradiated at our department, in an attempt to develop an effective treatment policy for this disease. MATERIALS AND METHODS: Twenty-nine patients with 53 lesions were treated between 1968 and 1993. Total irradiation doses were 4 to 60 Gy(median 40 Gy) with daily fractions of 2 Gy or less, and 16 to 51 Gy(median 30 Gy) with daily fractions greater than 2 Gy. Evaluated were 59 symptoms, including pain (68%), neurological abnormalities (15%), and masses (28%). RESULTS: Symptomatic remission was obtained in 33 of 36 (92%) lesions with pain, 6 of 8(75%) with neurological abnormalities, and 13 of 15(87%) mass lesions. Pain was partially relieved at a median TDF of 34, and completely at a median TDF of 66(equivalent to 40-42 Gy with daily fractions of 2 Gy). CONCLUSIONS: Radiation therapy is an effective and palliative treatment method for symptomatic multiple myeloma. However, the treatment seems to require higher radiation doses than those reported to obtain adequate relief of symptoms

Radiotherapy in the treatment of multiple myeloma.

Bosch A,  Int J Radiat Oncol Biol Phys 1988 Dec;15(6):1363-9

Department of Radiation Oncology, Oncologic Hospital, Puerto Rico Medical Center, Hato Rey.

Fifty-nine patients with multiple myeloma referred for treatment of painful bony lesions received irradiation to 95 local areas, and 16 of the 59 were irradiated using hemibody techniques. Pain relief was obtained in practically all of the irradiated regions. Most local areas were treated to doses of 3000 cGy in 10 to 15 fractions. Patients with generalized pain due to multiple site involvement were treated with single dose hemibody irradiation, to doses of 600 cGy to the upper hemibody, and of 800 cGy to the lower hemibody. This treatment was well tolerated and side effects minimal. Median survival from diagnosis was 30 months and the survival at 1, 3, and 5 years was 80%, 42%, and 12% respectively.

Multiple myeloma of an extremity: must the entire bone be treated?

Catell D,  Int J Radiat Oncol Biol Phys 1998 Jan 1;40(1):117-9

Division of Radiation Oncology, NYU Medical Center, New York 10016, USA.

PURPOSE/OBJECTIVE: Radiation of the entire shaft of a long bone affected by multiple myeloma (MM) is often advocated to prevent recurrent disease in the bone remote from the symptomatic site. Our standard of care has been to irradiate only the symptomatic area. We investigated the pattern of recurrence in patients treated in this manner. METHODS AND MATERIALS: 163 patient with MM were treated between 1971 and 1994. Twenty-seven patients received treatment to a long bone with 41 sites irradiated (17 humeri, 22 femurs, 1 radius, 1 ulna). The most common long bone treated was the femur. All patients were treated with megavoltage therapy. The symptomatic lesion, plus a margin of 1-2 cm was treated with no attempt to treat the entire shaft. Mean radiation dose was 27.82 Gy (range 6.00-44.80 Gy). The length of the field was measured in centimeters and expressed as both an absolute (AL) and relative (RL) length (i.e., percentage of total length of bone). RESULTS: The mean total AL and RL for femur fields was 18 cm and 42%, respectively. For the humerus, the AL and RL were 20 cm and 68%, respectively. Only four patients developed progressive disease in the same bone but outside the previously irradiated field. In three of the four patients the RL was between 20 and 30%. The dose of radiation given to these patients was 12.50, 21.00, 30.00, and 35.00 Gy. In all of these four cases, treatment of progressive disease in adjacent sites provided effective palliation of symptoms. CONCLUSION: Radiation therapy to the symptomatic portion of a long bone affected by MM is effective for palliation. Symptomatic recurrence out of the irradiated field is uncommon and can be effectively treated. Potential benefits of this approach include irradiation of less normal marrow and elimination of use of pairs of fields or extended distance treatment to cover the entire femur.

Clinical course of solitary extramedullary plasmacytoma.

Liebross RH, Radiother Oncol 1999 Sep;52(3):245-9

Department of Radiation Oncology, The University of Texas, M.D. Anderson Cancer Centre, Houston 77030, USA.

BACKGROUND AND PURPOSE: Solitary extramedullary plasmacytoma (EMP) represents a rare category of malignant disease on which there are limited data in regard to diagnosis, staging and natural history. This study attempted to clarify the clinical course of solitary extramedullary plasmacytoma after radiation or surgical therapy given with curative intent. MATERIALS AND METHODS: The diagnosis was based on a mass of clonal plasma cells separate from bone or bone marrow without evidence of occult disease elsewhere. Between 1963 and 1996, 22 previously untreated patients with an EMP were diagnosed. Disease presented in the head or neck in 86%, usually in the nasal cavity (NC) or maxillary sinus (MS), and in these areas local bone destruction was found in 10 of 11 patients. Among all patients, serum myeloma protein was present in three patients (14%) and Bence Jones protein alone was found in two patients (9%). Radiation therapy was the sole treatment for 18 of 22 patients, and the median radiotherapy dose was 50 Gy (range, 40-60 Gy); five of seven patients with an EMP of oral cavity (OC), oropharynx (OP), nasopharynx (NP), parotid or larynx also received elective neck irradiation. Two patients underwent surgery plus postoperative irradiation of a plasmacytoma of the sigmoid colon or pleura, and two patients had resection alone of a plasmacytoma of the colon or cervical lymph node. RESULTS: Local control was achieved in 21 of 22 patients (95%), and disease never recurred in regional nodes. Disappearance of myeloma protein occurred in three of five patients with an evaluable abnormality. Multiple myeloma developed in seven patients (32%), all within 5 years. The 5-year rate of freedom from progression to multiple myeloma was 56% and the median survival was 9.5 years. CONCLUSION: Radiation therapy achieved excellent locoregional control of EMP with an approximate cure fraction of 50%.

The role of radiation therapy in the treatment of solitary plasmacytomas.

Mayr NA, Radiother Oncol 1990 Apr;17(4):293-303

Department of Radiology, University of Iowa College of Medicine, Iowa City 52242-1059.

Between 1960 and 1985, 30 patients with solitary plasmacytomas were treated with radiotherapy at the University of Iowa: 13 patients with extramedullary plasmacytomas (EMP) and 17 with solitary plasmacytomas of bone (SPB). The local control rates were 92% for patients with EMP and 88% for those with SPB. Two of nine patients (22%) with EMP treated to the primary tumor only developed regional lymph node metastasis, indicating the need for elective irradiation of this area. The most common pattern of failure in both groups was progression to multiple myeloma. This occurred in 23% of the patients with EMP and 53% of those with SPB. The time course of progression to multiple myeloma differed for the two groups. All of those who progressed to multiple myeloma in the EMP group did so within 2 years, whereas a significant number of those in the SPB group progressed more than 5 years after initial therapy. None of five patients who received adjuvant chemotherapy in the SPB group progressed to multiple myeloma, compared to 75% (9/12) of the patients who did not receive chemotherapy.

Plasmacytomas of the head and neck.

Miller FR, Otolaryngol Head Neck Surg 1998 Dec;119(6):614-8

Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Plasmacytomas are rare tumors that often appear in the head and neck region and are characterized by a monoclonal proliferation of plasma cells. On both clinical presentation and pathologic examination these tumors may be confused with more common tumors of the head and neck. The purpose of this article is to review our experience with these rare neoplasms, with emphasis on clinical, pathologic, and therapeutic features. On retrospective chart review, we identified 20 patients with the diagnosis of plasmacytoma of the head and neck region at the Cleveland Clinic Foundation between 1976 and 1993. Records were reviewed with regard to initial symptoms, location of the neoplasm, diagnostic evaluation, treatment modalities, and survival. Of the 20 cases we identified, the tumor arose in the sinonasal/nasopharyngeal region in 11 (55%). Two cases (10%) represented medullary plasmacytomas, arising in the clavicle and presenting as supraclavicular masses. The mean follow-up was 60.2 months (range 6 to 131 months). In 15 of the 20 cases, immunohistochemistry staining for immunoglobulin light chain production was conducted. One of the two cases (50%) classified as medullary plasmacytoma demonstrated conversion to multiple myeloma, whereas only 2 of 18 cases of extramedullary plasmacytoma (11%) converted to multiple myeloma. The primary modality of treatment was radiation therapy with typical doses of 4500 to 6000 cGy. Kaplan-Meier survival estimates demonstrated 95% survival at 1 year, 82% survival at 5 years, and 10-year estimated survival of 72%. Plasmacytomas of the head and neck region are rare and on initial evaluation must be distinguished from multiple myeloma. The diagnostic evaluation includes appropriate radiologic and pathologic studies including immunohistochemistry. Despite the typical presentation as a locally destructive tumor, plasmacytomas are highly radiosensitive, and 70% to 80% survival may be obtained with the use of radiotherapy. Patients with plasmacytomas require long-term follow-up to detect conversion to multiple myeloma.

Solitary plasmacytoma of bone and soft tissue.

Bolek TW, Int J Radiat Oncol Biol Phys 1996 Sep 1;36(2):329-33

Department of Radiation Oncology, University of Florida, College of Medicine, Gainesville, USA.

PURPOSE: This retrospective review evaluates the results of radiotherapy used for curative intent in the management of solitary plasmacytoma. METHODS AND MATERIALS: Between August 1963 and January 1993, 37 patients with a solitary plasmacytoma were treated with curative intent at the University of Florida. Criteria for inclusion in the study were (a) a biopsy-proven plasmacytoma, (b) no tumor in the bone marrow on biopsy, and (c) no evidence of disseminated disease on skeletal survey. The primary site was osseous in 27 patients and extramedullary in 10 patients; 9 of the 10 extramedullary lesions were located in the upper respiratory passages. Treatment consisted of primary radiotherapy in all but one patient, who received surgical resection alone. Two patients also received adjuvant chemotherapy. The median radiation dose was 43.2 Gy in 1.8-Gy fractions. Absolute survival, progression to myeloma, and local control rates were calculated using the Kaplan-Meier method. A multivariate analysis was performed for prognostic factors predictive of absolute survival. RESULTS: Multivariate analysis revealed tumor type (osseous vs. extramedullary) to be predictive of absolute survival (p = 0.12). Factors not predictive of survival were age, sex, use of chemotherapy, immunoglobulin level, and type of immunoglobulin elevated. Patients with osseous tumors had a lower survival rate than those with extramedullary tumors (55% vs. 80% at 10 years, p = 0.06). Multiple myeloma was more likely to develop in patients with osseous tumors (54% vs. 11% at 10 years, 100% vs. 33% at 15 years, p = 0.03). Of patients in whom multiple myeloma developed, those with osseous tumors had a poorer survival rate after development of myeloma (32% vs. 100% at 5 years, p = 0.11). Local relapse developed in 1 patient with an osseous tumor 10 months after treatment with 28.3 Gy in 14 fractions; this was controlled with an additional 28.3 Gy in 10 fractions. Local failure did not develop in any patient with an extramedullary tumor. CONCLUSIONS: Radiotherapy is an effective local treatment for solitary plasmacytoma. Osseous tumors were found to have a poor prognosis compared with extramedullary tumors.

Solitary plasmacytoma of bone: treatment, progression, and survival.

Chak LY,  J Clin Oncol 1987 Nov;5(11):1811-5

Department of Therapeutic Radiology, Stanford University, Medical Center, CA.

Twenty patients with solitary plasmacytoma of bone were treated by radiation therapy. Local control was achieved in 19 and most patients developed systemic myeloma. To evaluate disease progression, 65 patients, including 45 from published series, were analyzed. Younger patients seemed less likely to progress (P = .06), but other clinical characteristics including site of involvement and paraprotein status did not influence progression. After dissemination, patients had a clinical course similar to patients with stage I myeloma, with a median survival of 47 months. Overall, patients with solitary plasmacytoma of bone had an indolent course of disease, with a median survival of 10.7 years and a 5-, 10-, and 20-year survival of 75%, 52%, and 37%, respectively.

Solitary plasmacytoma of bone: Mayo Clinic experience.

Frassica DA, Int J Radiat Oncol Biol Phys 1989 Jan;16(1):43-8

Mayo Clinic, Rochester, MN 55905.

A review of 46 cases of solitary plasmacytoma of bone was undertaken in an attempt to better define the clinical features and prognostic indicators associated with this disease. Criteria for inclusion in the study included the following: (a) solitary lytic bone lesion on skeletal survey; (b) histologic confirmation of the lesion; and (c) bone marrow plasmacytosis of less than 10 percent. Patients with extramedullary plasmacytomas and osteosclerotic lesions were excluded. All patients were evaluated with serum and urine protein studies at the time of diagnosis. The median follow-up was 90 months with a minimum of 30 months. Fifty-four percent of the lesions involved the vertebral column. The thoracic spine was the single most commonly involved site (13/46 patients). The initial lesion was treated with radiotherapy in all but three patients in whom complete surgical resection was achieved. Total doses ranged from less than 20 Gy to 70 Gy with a median of 39.75 Gy. Overall, 54% developed multiple myeloma, 2% failed with new bone lesions without multiple myeloma, and 11% developed local recurrences. No patient receiving 45 Gy or more to the solitary lesion had a local failure. While the median time to progression was 18 months, 23% of the failures occurred after 60 months. The five local failures occurred at 7, 12, 18, 40, and 114 months. The overall survival was 74% at 5 years and 45% at 10 years. The 5- and 10-year disease-free survivals, however, were 43 and 25%, respectively. Evidence of abnormal serum and/or urine protein was found in 25 of 46 patients. Neither survival nor disease-free survival was significantly influenced by the presence of abnormal proteins even if they persisted after irradiation.

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