Primary bone lymphoma: treatment results and prognostic factors with long-term follow-up of 82 patients.

Long-term results of combined modality therapy in primary bone lymphomas.

Fidias P, Spiro I, Sobczak ML, Nielsen GP, Ruffolo EF, Mankin H, Suit HD, Harmon DC  Int J Radiat Oncol Biol Phys 1999 Dec 1;45(5):1213-8

Department of Medical Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, USA. PFidias2@Partners.org

PURPOSE: To report the Massachusetts General Hospital experience in the management of patients with primary bone lymphoma (PBL) treated with combined modality therapy (CMT). METHODS AND MATERIALS: Records from 37 eligible patients were reviewed. Two patients were treated with complete resection of the tumor, while 35 patients underwent radiation therapy with a median total dose of 54 Gy (range 38.35-66.5). All patients received combination chemotherapy, which contained doxorubicin in 33 cases. We compared the current data with our previous experience in patients treated with local measures only. RESULTS: Actuarial disease-free survival (DFS) at 5 and 10 years is 78% and 73%, respectively, while overall survival (OS) is 91% and 87%, respectively. No local failures were seen. Pathologic fracture at presentation influenced DFS (p = 0.005) and OS (p = 0.017) adversely. OS was compromised in patients older than 60 years (p = 0.059) and DFS in patients with pelvic primaries (p = 0.015). CMT was associated with improved DFS (p = 0.0008) and OS p = 0.0001) compared to our historical controls. Ten patients (27%) developed complications requiring orthopedic procedures following completion of therapy at a median of 25.5 months (range 4-228). CONCLUSION: Patients with PBL have a favorable outcome with CMT, which appears superior to radiation therapy alone. Late complications can be seen, especially in weight-bearing bones.

Int J Radiat Oncol Biol Phys 1997 Mar 15;37(5):1087-93

Localized primary malignant lymphoma of bone.

Dubey P, Ha CS, Besa PC, Fuller L, Cabanillas F, Murray J, Hess MA, Cox JD

Department of Radiotherapy, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

PURPOSE: A single institution's experience with the treatment of localized primary malignant lymphoma of bone (PLB) was analyzed to identify major prognostic factors, toxicity, and optimal treatment for this rare malignancy. METHODS AND MATERIALS: A retrospective analysis of 45 previously untreated patients with Ann Arbor stage IE and IIE PLB from 1967 to 1992 was undertaken. All histopathologic material was reviewed. Irradiated patients received at least 40 Gy. Systemic chemotherapy was generally doxorubicin based. Overall survival (OS), progression free survival (PFS), and disease-specific survival (DSS) were calculated actuarially. RESULTS: Histologically, there were 41 diffuse large cell, 2 diffuse mixed cell, 1 lymphocytic, and 1 lymphoblastic lymphomas. International Index scores were assessed on 43 patients. Thirty-six patients were treated with chemotherapy and radiation (CMT), five patients were treated with radiation only, and four patients were treated with chemotherapy only. Univariate analysis revealed significantly improved 5-year OS for those patients who had International Index scores of 0 vs. scores of 1 or 2 (85 vs. 53%, respectively, p = 0.004). Analysis failed to demonstrate a difference in OS, PFS, or DSS when comparing radiotherapy alone versus CMT, stage IE vs. stage IIE, or axial skeleton involvement vs. extremities. CONCLUSION: The outcome of patients with PLB is relatively favorable in the era of CMT. Doses of radiation in the range of 46 Gy provide optimal local control with an acceptable rate of complications. The International Index is a valid prognostic tool for PLB.

Nebr Med J 1990 Nov;75(11):303-6

Primary lymphoma of bone.

Chin HW, McGuire MH, Block M, Frank AR, Boman BM, Mailliard JA

Department of Radiation Oncology, Creighton University School of Medicine, Omaha, Nebraska 68131.

Primary lymphoma of bone is a rare clinical entity that accounts for less than one per cent of all non-Hodgkin's lymphomas. Although they occasionally present as a solitary lesion in bone, lymphoma involving bone is a manifestation of disseminated disease in many instances. All patients initially found to have a solitary lymphoma of bone need to be thoroughly investigated for systemic disease because more than half of the patients presenting with initially solitary bone lesions are found to have systemic disease involving lymph nodes and/or other organs. Choice of therapeutic management is based on the stage of disease. Stage I-E primary lymphoma of bone can be controlled in 70-90% of cases using local radiation therapy alone if adequate radiation doses are used. Patients with advanced disease should be treated with combination chemotherapy in addition to local radiotherapy. Loeffler et al reported long-term survival results of 90% 8-year actuarial overall survival rate for children with primary lymphoma of bone who received combined therapy with radiation and chemotherapy (adriamycin, prednisone and oncovin). The actuarial lymphoma-free survival rate was 100% at eight years. Regardless of stage of the disease, radiation treatment to the primary tumor appears to be critical for adequate local control of disease as well as rapid symptomatic relief.

Int J Radiat Oncol Biol Phys 1994 Jan 15;28(2):363-72

Treatment of stage IE primary lymphoma of bone.

Fairbanks RK, Bonner JA, Inwards CY, Strickler JG, Habermann TM, Unni KK, Su J

Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905.

PURPOSE: A retrospective analysis was performed to assess the efficacy of various treatments of Stage IE primary non-Hodgkins lymphoma of bone. METHODS AND MATERIALS: Sixty-three patients with Stage IE primary non-Hodgkins lymphoma of bone (single osseous focus) were seen at our institution between the years 1970 and 1989. Information was obtained regarding each patients' presentation and clinical course. The histology was reviewed in all patients. Modern immunohistochemical stains were performed on each case with available paraffin-embedded tissue. RESULTS: The histologic classification of the tumors was as follows: 43 diffuse large cell, 13 diffuse mixed cell, 3 small noncleaved, and 4 unclassified. The most common presenting symptom was pain (97%) and the following bony sites were involved: 36 long bone, 9 flat bone, 13 spine, and 5 pelvis. Of the 63 cases, 50 were treated with radiation alone, 10 with chemotherapy and radiation, 2 with chemotherapy alone, and 1 with surgery alone. Univariate analysis revealed a suggestion of an improved 5-year disease-free survival for patients treated with chemotherapy and radiation vs. radiation alone (90% vs. 57% respectively, p = .08). Multivariate analysis (controlling for extent of initial evaluation, extent of pathological evaluation and other potential prognostic factors) showed that neither treatment resulted in superior outcome with respect to disease-free survival, disease specific survival, or overall survival, however, doses of radiation greater than 4000 cGy resulted in improved overall survival compared to lower doses (p = 0.01). CONCLUSION: This study supports the use of primary RT (> 4000 cGy) for Stage IE PLB, however, the addition of chemotherapy to the radiotherapeutic management may decrease the initial relapse rate of some patients. Future studies should address this question.

Br J Cancer 1992 Sep;66(3):603-6

Localised lymphoma of bone: prognostic factors and treatment recommendations. The Princess Margaret Hospital Lymphoma Group.

Rathmell AJ, Gospodarowicz MK, Sutcliffe SB, Clark RM

Princess Margaret Hospital, Department of Radiation Oncology, Toronto, Ontario, Canada.

Twenty seven adult patients with newly diagnosed non-Hodgkin's lymphoma localised to either bone (Stage IE) or bone and regional lymph nodes (Stage IIE) were treated between 1967 and 1988. Median age was 53 years and the commonest histology (21 patients) was diffuse histiocytic lymphoma. Twenty-four patients were treated radically: 15 with radiation therapy (XRT) alone and nine with chemotherapy plus radiation therapy (CMT). The cause specific survival for these patients was 56% at 5 years and 40% at 10 years. Survival was significantly better for patients treated by CMT (88% at 5 years) as compared to XRT alone (40% at 5 years, P = 0.03) and for age less than 60 (72% at 5 years) compared to greater than or equal to 60 (30% at 5 years, P = 0.018). Relapse-free rate was 27% at 5 years with XRT alone and 89% with CMT (P = 0.01). Risk factors for loco-regional relapse (seven cases) included: large tumour bulk, treatment by XRT alone and use of 'limited' radiation fields. No radiation dose-response relationship could be identified in this study. Long term local control and survival for localised lymphoma of bone were excellent after treatment by CMT but XRT alone was associated with unacceptably high local and distant failure rates.

J Chemother 1991 Jun;3(3):189-93

Primary lymphoma of bone: long term results in patients treated with vincristine--adriamycin--cyclophosphamide and local radiation.

Bacci G, Ferraro A, Casadei R, Barbieri E, Avella M, Ferrari S, Bertoni F, Picci P, Ruggieri P, Biagini R

Bone Tumor Center-Istituto Rizzoli, Bologna, Italy.

Primary lymphoma of bone (PLB) is an unusual but well-recognized extranodal presentation of non-Hodgkin's lymphoma. In most series treatment with radiotherapy alone results in a cure rate of approximately 40%. Between January 1972 and December 1982, 26 patients with biopsy proven PLB were treated at the Rizzoli Institute with radiotherapy (4000-5,500 rad) and chemotherapy (vincristine, cyclophosphamide and adriamycin). The minimal clinical staging included complete blood cell counts and serum chemistries, bone radiography, full lung tomography, isotope bone scan, bone marrow biopsy and bipedal lymphoangiograms. At a median follow-up of 13 years (8.5-18.5) there were only three relapses (2 cases of meningeal involvement and 1 recurrence in another bone). No local recurrences nor second tumor in the irradiated field were observed. We conclude that the addition of chemotherapy to radiotherapy results in an excellent cure rate for patients with PLB.

Cancer 1986 Dec 15;58(12):2646-55

Malignant lymphoma of bone.

Ostrowski ML, Unni KK, Banks PM, Shives TC, Evans RG, O'Connell MJ, Taylor WF

A total of 422 patients with malignant lymphoma of bone who were seen at the Mayo Clinic from 1907 through 1982 were placed into four major groups based on stage of disease. There was one group with primary lymphoma of bone, one group with multifocal osseous lymphoma, and two groups with lymphoma of bone and nodal or soft tissue (or both) disease. The last-mentioned two groups were separated on the basis of time of onset of osseous lymphoma in relation to the nonosseous disease. The stage of disease was the single most important prognostic indicator of overall survival in malignant lymphoma of bone. The 5- and 10-year survival rates were, respectively, 58% and 53% for patients with primary bone lymphoma, 22% and 12.5% for patients with bone and nodal or soft tissue (or both) disease, and 42% and 35% for patients with multifocal osseous disease. Features having no significant prognostic value were sex of the patient, histologic grade of the lymphoma (according to the Working Formulation and the Kiel system), and presence of T-cell features or cleaved cells (or both). This study is not able to adequately address efficacy of treatment. In fact, treatment may be very important in outcome.

Radiother Oncol 1987 Jun;9(2):137-45

The management of primary lymphoma of bone.

Mendenhall NP, Jones JJ, Kramer BS, Hudson TM, Carter RL, Enneking WF, Marcus RB Jr, Million RR

From October 1962 through April 1982, 21 patients with the diagnosis of primary lymphoma of bone (18 monostotic, stages IE and IIE; 3 polyostotic) were treated with curative intent. A combination of chemotherapy and radiation therapy was used in 11 patients, local treatment alone in 9 patients, and chemotherapy alone in one patient. Overall 5-year survival for the patients treated with curative intent was 56%. Standard work-up has changed over the 20-year study period. Five-year survival for the subset of eight stage I and II patients with full pretherapy staging was 83%. Prognosis was significantly correlated with extent of pretherapy staging. Treatment parameters that also seemed to predict outcome were the aggressiveness of chemotherapy and the use of irradiation or surgery for local-regional disease; the only local failure occurred in the patient who received chemotherapy alone. Complications of radiation therapy alone and in combination with chemotherapy are discussed and correlated with irradiation dose. Radiation therapy techniques are described, and a management approach is recommended.

J Surg Oncol 1990 Aug;44(4):229-33

Primary lymphoma of bone: experience of 39 cases at the Tata Memorial Hospital, India.

Susnerwala SS, Dinshaw KA, Pande SC, Shrivastava SK, Gonsalves MA, Advani SH, Gopal R

Department of Radiation Oncology, Tata Memorial Hospital, Parel, Bombay, India.

Primary lymphoma of bone (PLB) is an uncommon clinical entity and a rare presentation of non-Hodgkin's lymphoma. At the Tata Memorial Hospital, over a period of 10 years from 1976 to 1985, 39 cases with a diagnosis of PLB were seen. Twenty-seven cases completed the prescribed treatment and were evaluable for treatment response. Eight patients (21%) presented in clinical stage I (E), four patients (10%) in stage II (E), and 27 patients (69%) in stage IV (E). All of the evaluable patients except two were treated with combination chemotherapy, which consisted of cyclophosphamide, vincristine, and prednisolone in 18 patients, and seven patients received Adriamycin in addition. The majority of patients received six courses of chemotherapy extending over 8 to 12 months. External radiotherapy was given to all except one patient, who had surgery as local treatment. Five patients had generalised relapse, one of which had in addition a local relapse. Five were resistant to treatment. Overall and disease-free survival by Kaplan-Meier method at 60 months are 66% and 56%, respectively.