[en] 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

[en] Purpose/Objectives: The earliest stages of Hodgkin's disease are associated with excellent short term survival with radiation therapy. This has led to controversies regarding pretreatment evaluation, extent of treatment fields, a possible role of chemotherapy and the importance of several prognostic factors. Long term results were sought to address these controversies. Materials and methods: A retrospective study was conducted of patients with stage I Hodgkin's disease treated at the MD Anderson Cancer Center from 1967 through 1987. The median age at presentation of 131 patients was 31 years and the male to female ratio was 1.9. Pretreatment evaluation included lymphangiography and bone marrow aspiration and biopsy in all patients. Laparotomy was performed in 97 out of the 131 patients (74%). There were 120 patients with supradiaphragmatic presentations versus 11 with infradiaphragmatic involvement. Only 3 patients had B symptoms (2.29%). Histologic subtypes of the disease included lymphocyte predominant 19.8%, nodular sclerosing 38.2% and mixed cellularity 41.9%. All patients were treated with radiotherapy and 14 out of 131 patients had combination chemotherapy as part of their initial treatment. Radiotherapy techniques included involved/regional field 49.6%, extended field 41.2% (mantle or inverted Y) and subtotal nodal irradiation. Follow up extended from a minimum of 7 years to 27 years, with a median period of observation of 13.25 years. Results: Median survival was 15.8 years. The 20 and 25 year survival rates were 64% and 61% respectively. The only factor important for survival was age greater than 40 years at diagnosis (P < 0.001). Out of 36 deaths 11 were the result of active Hodgkin's disease and the remaining 25 occurred because of intercurrent disease or treatment related causes. Staging laparotomy was related to prolonged survival, but significantly more patients staged with laparotomy were younger than 40 years of age (P = 0.026). Median freedom from progression was 13.1 years and the 3, 10 and 25 year freedom from progression were 86.2%, 76.2% and 67.8% respectively. Out of 35 relapses, 5 (14.2%) occurred beyond 10 years. Women had significantly higher freedom from progression (P=0.037) than men. Age, Histology, bulk of disease, site of involvement including the mediastinal presentations and the addition of chemotherapy did not influence the freedom of progression. Although very few patients ((12(131))) received subtotal nodal irradiation, the freedom from progression at 10 years was 92% for this group versus 67% for the group of patients that were treated with more limited techniques (P=0.11). Conclusions: Treatment with Radiotherapy for patients with stage I Hodgkin's disease leads to an excellent outcome. However, the patients require long term surveillance as late relapses are not rare. Age is the only factor that affects survival and sex affects freedom from progression. Subtotal nodal irradiation may affect freedom from progression and further investigation of this treatment is justified

[en] Purpose: Levels of spontaneous apoptosis predict for tumor responsiveness to radiation and chemotherapy in various animal systems. Oncogenes belonging to the bcl-2 family have been found to govern apoptosis, and bcl-2 has been shown to convey multi-drug resistance in lymphoma in vitro. To investigate the potential role of apoptosis and oncogenes involved in apoptosis as a predictors of response in human tumors, a retrospective review was undertaken of patients with Stage I and II follicular lymphoma in whom long term results were recently reported. Materials and Methods: The H and E slides of the initial specimens of 91 patients were obtained. All slides were reviewed by one pathologist (WCP) and representative sections were chosen. Twenty-four patients were treated with regional radiotherapy, 57 patients with multiagent chemotherapy and regional radiotherapy, and 10 patients with multiagent chemotherapy alone. Apoptotic index (AI) and mitotic index (MI) were determined for each tumor by counting the number of apoptotic bodies and mitotic cells present in 500 cells (100 cells in each of 5 follicles). Paraffin-embedded tissue was obtained for 52 of the initial specimens, and bcl-2, bax, and bcl-x status was determined by immunohistochemistry for these cases. The above parameters were correlated with overall survival (OS) and freedom from progression (FFP). Follow-up for living patients ranged from 51 to 212 months with a median value of 114 months. Results: The AI and MI values were low, ranging from 0 - 5.2% and 0 - 1.0%, respectively. The median AI value was 0.4%, and 63 patients had a MI of 0%. Patients who were treated with combined chemotherapy and radiotherapy had a higher FFP when their tumors had spontaneous levels of apoptosis of < 0.4% (73% vs 40% 10-year FFP; p=0.017). In addition, patients treated with combined chemotherapy and radiotherapy had an improved OS when AI was < 0.4% (83% vs 58% 10-year OS; p = 0.026). Among patients who were treated with radiotherapy alone, AI did not correlate with FFP, but patients in this group whose tumor had a MI > 0 had an improved FFP (83% vs 27% 10-year FFP; p=0.05). Bcl-2, bax and bcl-x staining was positive for 41, 48, and 47 initial specimens, respectively. No correlation of bcl-2, bax or bcl-x staining with clinical outcome was found. Differences in staining pattern are apparent and will be characterized and correlated with clinical outcome. Conclusion: The level of spontaneous apoptosis predicted for FFP and OS in patients with localized follicular lymphoma treated with chemotherapy and radiation while the level of mitosis predicted for FFP in patients treated with radiation only

[en] Purpose: The earliest stages of Hodgkin's disease are associated with excellent short-term survival with radiation therapy. This has led to controversies regarding pretreatment evaluation, the extent of irradiation, the role of chemotherapy, and the relative importance of prognostic factors. Long-term results were sought to address these controversies. Methods and Materials: A retrospective study was conducted of patients with Stage I Hodgkin's disease treated at the M. D. Anderson Cancer Center from 1967 through 1987. The median age at presentation of 145 patients was 31 years, and the male-to-female ratio was 1.8. Pretreatment evaluation included lymphangiography and bone marrow aspiration and biopsy in all patients. Laparotomy was performed in 101 of the 145 patients (70%). There were 133 patients with supradiaphragmatic presentations; 12 patients had infradiaphragmatic adenopathy. Only five patients had B symptoms (3.5%). Histologic subtypes of the disease included lymphocyte predominance 17.9%, nodular sclerosis 40.7%, mixed cellularity 40.7%, and one unclassified Hodgkin's disease with primary splenic involvement. All patients were treated with radiotherapy, and 16 (11%) also received combination chemotherapy as part of their initial treatment. Radiotherapy techniques included involved/regional field in 49%, extended field in 42.7% (mantle or inverted Y), and subtotal nodal irradiation in 8.3%. Follow-up extended from a minimum of 30-339 months, with a median period of observation of 16.5 years. Results: The median survival was 13.7 years. The 10- and 20-year survival rates were 83% and 66%, respectively. The only factor important for decreased survival was age >40 years at diagnosis (p < 0.0001). Out of 43 deaths, 11 were the result of Hodgkin's disease and the remaining 32 resulted from intercurrent disease, including treatment-related causes. Median freedom from progression was 10.5 years, and the 10- and 20-year freedom from progression were 76% and 69%, respectively. Out of 39 relapses, 5 (13%) occurred beyond 10 years. Women had higher freedom from progression (p = 0.0534) than men. Age, histology, bulk of disease, site of involvement including the mediastinal presentations, and the addition of chemotherapy did not influence the freedom of progression. Although very few patients (12 of 145) received subtotal nodal irradiation, the freedom from progression at 10 years was 91.7% for this group versus 64.7% for the group of patients who were treated with more limited techniques. Conclusion: Treatment with radiation therapy for patients with Stage I Hodgkin's disease leads to an excellent outcome, but patients require long-term surveillance as late relapses are not rare. Age is the only factor that affects survival, and gender marginally affects freedom from progression. Subtotal nodal irradiation may improve freedom from progression; further investigation of this treatment is justified

[en] Purpose: Radiation therapy results in excellent short-term survival in patients with early-stage Hodgkin's disease. However, the optimal therapeutic scheme that achieves the highest disease-free survival with the minimum long-term toxicity is yet to be determined. An analysis of the patterns of failure and late complications after radiation therapy was conducted to address this question. Methods and Materials: A retrospective study was conducted of 145 patients with Stage I Hodgkin's disease treated at M.D. Anderson Cancer Center from 1967 through 1987. Follow-up extended from a minimum of 30 to 339 months, with a median period of observation of 16.5 years. All the patients were treated with radiation therapy and, and 16 received combination MOPP-based chemotherapy as part of their initial treatment. The radiotherapy technique, was involved/regional in 71 (49%), extended in 62 (43%), and subtotal nodal irradiation in 12 patients. The median total dose was 40 Gy. Results: The actuarial freedom from progression at 10 and 20 years was 76% and 69%, respectively. Forty of 145 patients relapsed (27.6%). The site of primary disease was cervical adenopathy in 30 (75%), axillary in 7 (17.5%), mediastinal in 2 patients and subdiaphragmatic in one patient. Twenty-two patients were treated with involved/regional technique (55%), 17 with extended (42.5%), and 1 with subtotal nodal irradiation technique. There were three in field and four marginal recurrences. Six relapses occurred in non-irradiated nodal regions at the same side of the diaphragm and 17 in non-irradiated transdiaphragmatic lymph nodes (57.5%). Nine patients (22.5%) relapsed with visceral disease. Nineteen patients (47.5%) relapsed within the first 2 years, 15 (37.5%) 3 to 10 years after diagnosis and the remaining 6 (15%) after 10 years. Eleven of 40 patients died of disease after the first or subsequent relapses (27.5%). Three of six patients with late relapses had progression in viscera but only two died with disease. Thirty-eight of 145 patients developed late toxicity from the treatment (26.2%). Twenty-three patients experienced ischemic heart disease (15.9%), only 13 of whom received mediastinal irradiation (9%). Fifteen patients developed secondary malignant solid tumors (10.3%). Nine of those (6.2%) occurred within the irradiation field (two were also treated with chemotherapy). Two additional patients, one of whom received chemotherapy as part of the initial treatment, died of acute myelogenous leukemia. Non-Hodgkin's lymphoma and lung cancer were the most common second malignancies. Conclusions: Limited field radiotherapy results in a significant number of relapses in non-irradiated, especially transdiaphragmatic lymph nodes. Subtotal nodal irradiation can prevent some relapses and therefore improve freedom from progression. Careful design of the treatment fields may decrease the risk of morbidity and mortality from coronary artery disease and second malignancies in early-stage Hodgkin's disease. Careful long-term surveillance may permit early detection and management of late relapses and treatment complications

[en] Purpose: Radiation therapy results in excellent short term survival in patients with early stage Hodgkin's disease. However, the optimal therapeutic scheme that achieves prolonged freedom from progression with the minimum long term toxicity is yet to be determined. An analysis of the patterns of failure and late complications after radiation therapy was conducted to address this question. Materials and Methods: A retrospective study was conducted of 145 patients with stage I Hodgkin's disease treated at M D Anderson Cancer Center from 1967 through 1987. Follow up extended from a minimum of 30 to 339 months, with a median period of observation of 16.5 years. All the patients were treated with radiation therapy and 16 received combination MOPP based chemotherapy as part of their initial treatment. The radiotherapy technique, was involved/regional in 71 (59%), extended in 62 (43%) and subtotal nodal irradiation in 12 patients. The median total radiotherapy dose was 40 Gy. The median freedom from progression was 10.9 years. Results: Thirty eight of 145 patients relapsed (26.2%). The site of primary disease was cervical adenopathy in twenty eight (73.7%), axillary in 7 (18.4%) and mediastinal and subdiaphragmatic adenopathy in 2 patients. Twenty one patients were treated with involved/regional technique (55.3%), 16 with extended (42.1%) and one with subtotal nodal irradiation technique. There were 3 in field and 4 marginal recurrences. Six relapses occurred in non-irradiated nodal regions at the same side of the diaphragm and 16 in non- irradiated transdiaphragmatic lymph nodes (57.9%). Nine patients (23.7%) relapsed with visceral disease. Nineteen patients (50%) relapsed within the first three years, 14 (36.8%) three to ten years after the diagnosis and the remaining 5 (13%) after ten years. Twelve of 38 patients died of disease after the first or subsequent relapses (31.5%). Three of five patients with late relapses had progression in viscera but only two died with disease. Thirty five of 145 patients developed late toxicity from the treatment (24.1%). Twenty patients experienced ischemic heart disease (13.7%) but only 12 received mediastinal irradiation (8.2%). Fifteen patients developed secondary malignant tumors (10.3%). Nine of those (6.2%) occurred within the irradiation field (two were also treated with chemotherapy). Two patients, one of which received chemotherapy as part of the initial treatment, died of acute myelogenous leukemia. Non Hodgkin's lymphoma and lung cancer were the most common second malignancies. Conclusions: Limited field radiotherapy results in a significant number of relapses in non-irradiated, especially transdiaphragmatic lymph nodes. Subtotal nodal irradiation may prevent those and therefore improve freedom from progression. Careful design of the treatment fields may decrease the risk of morbidity and mortality from coronary artery disease and second malignancies in early stage Hodgkin's disease. Long term follow up may result in early detection and management of late relapses and treatment complications

[en] Purpose: The prognostic significance of spontaneous levels of apoptosis and Bcl-2, Bax, and Bcl-x protein expression in follicular center lymphoma (FCL) is unknown. The objectives of this retrospective study were (1) to investigate the relationship between pretreatment apoptosis levels and long-term treatment outcome in patients with Stage I and II FCL; (2) to define the incidence and patterns of Bax and Bcl-x protein expression in human FC; and (3) to determine the relationship of Bcl-2, Bax, and Bcl-x expression with spontaneous apoptosis levels and clinical outcome in localized FCL. Methods and Materials: Between 1974 and 1988, 144 patients with Stage I or II FCL were treated. Hematoxylin and eosin (H and E) stained tissue sections of pretreatment specimens were retrieved for 96 patients. Treatment consisted of regional radiation therapy (XRT) for 25 patients, combined modality therapy (CMT) consisting of combination chemotherapy and XRT for 57 patients, and other treatments for 14 patients. Median follow-up for living patients was nearly 12 years. The apoptotic index (AI) was calculated by dividing the number of apoptotic cells by the total number of cells counted and multiplying by 100. Expression of Bcl-2, Bax, and Bcl-x proteins was assessed using immunohistochemistry. Results: The mean and median AI values for the entire group were 0.53 and 0.4, respectively (range: 0-5.2). The AI strongly correlated with cytologic grade, with mean AI values of 0.25 for grade 1, 0.56 for grade 2, and 0.84 for grade 3 (p < 0.0005; Kendall correlation). A positive correlation was present between grouped AI and grouped mitotic index (MI) (p = 0.014). For patients treated with CMT, an AI < 0.4 correlated with improved freedom from relapse (FFR) (p = 0.0145) and overall survival (OS) (p = 0.0081). An AI < 0.4 did not correlate with clinical outcome for the entire cohort or for patients receiving XRT only. Staining of tumor follicles for the Bcl-2 protein was positive, variable, and negative in 73%, 15%, and 12% of cases, respectively. Positive staining of tumor follicles was observed in 96% of cases for both the Bax and Bcl-x proteins. Expression of Bcl-2, Bax, or Bcl-x did not correlate with AI or clinical outcome. Conclusion: The level of spontaneous apoptosis in pretreatment specimens correlates with cytologic grade of FCL and is a significant predictor of FFR and OS for patients with localized FCL receiving CMT