[en] Purpose: To report long term follow-up results and analyze prognostic factors for overall and disease-free survival in patients with subdiaphragmatic stage I and II Hodgkin's disease. Methods and Materials: From September 1962 to April 1995, 109 patients presented to the M. D. Anderson Cancer Center with subdiaphragmatic Hodgkin's disease. The medical records of these patients were retrospectively reviewed. Twenty-two patients who received no treatment at M. D. Anderson Cancer Center or who had radiation therapy at other institutions were excluded. The remaining 87 patients formed the basis of this study. The median age of our group was 33 years with a male:female ratio of 3.3:1. The histological subtypes were nodular sclerosis in 21 (24.1%) patients, mixed cellularity in 31 (35.6%), lymphocyte predominence in 33 (37.9%), lymphocyte depletion in 1 (1.1%) and unclassified histology in 1 (1.1%). Thirty three (37%) patients underwent laparotomy, 74 (85.1%) had lymphangiography, and 35 (40.2%) had computerized tomography of the abdomen. Twenty two (25%) patients had more than three sites of nodal involvement at presentation, 56 (64.4%) had pelvic or abdominal disease, and 14 (18.4%) had bulky disease which was defined as disease with largest dimension ≥ 7 cm. Stage distribution was IA in 33.3%, IIA in 39.1%, and IIB in 27.6%. Sixty (69%) patients were treated with radiotherapy alone, 23 (26.4%) with chemotherapy and radiation, and 4 (4.6%) with chemotherapy alone. Results: The 10 and 20 year actuarial overall survival rates for all the patients were 74.6% and 55.3%, and the corresponding disease free survival rates were 72.4% and 67.5%, respectively. On univariate analysis, age, B symptoms, nodular sclerosis or mixed cellularity histology, and decreased albumin and hemoglobin level were statistically significant adverse pretreatment factors for overall survival. B symptoms, decreased albumin level, more than 3 sites of disease at presentation, and stage were statistically significant negative pretreatment prognostic factors for disease-free survival. Only B symptoms and decreased albumin level predicted worse outcome in both overall and disease-free survivals. Age, histology, and hemoglobin level were three independent risk factors for overall survival on multivariate analysis. An analysis of the pattern of failure revealed that majority of the patients with Stage II disease who did not receive mantle radiation failed in the supradiaphragmatic area. Late complications of radiation were infrequent. Conclusions: Long term follow up of this group of patients revealed similar overall and disease free long term survival as would be expected from supradiaphragmatic Hodgkin's disease. For patients with stage II disease, it is anticipated that supradiaphragmatic radiation therapy would improve the disease free survival

[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: To report long-term follow-up results and to analyze prognostic factors for overall and disease-free survival in patients with subdiaphragmatic Stage I and II Hodgkin's disease. Methods and Materials: From September 1962 to April 1995, 109 patients presented at the M. D. Anderson Cancer Center with subdiaphragmatic Hodgkin's disease. The medical records of these patients were retrospectively reviewed; 22 patients who received no treatment at the M. D. Anderson Cancer Center or who had radiation therapy at other institutions were excluded. The remaining 87 patients formed the basis of this study. The median age of our group was 33 years with a male: female ratio of 3.3:1. The histological subtypes were nodular sclerosis in 21 (24.1%) patients, mixed cellularity in 31 (35.6%), lymphocyte predominance in 33 (37.9%), lymphocyte depletion in 1 (1.1%) and unclassified histology in 1 (1.1%). Of the patients, 32 (36.8%) underwent laparotomy for diagnosis or staging purpose, 74 (85.1%) had lymphangiography, and 35 (40.2%) had computerized tomography of the abdomen and pelvis. Among the patients, 22 (25%) had more than three sites of nodal involvement at presentation, 56 (64.4%) had pelvic or abdominal disease, and 14 (18.4%) had bulky disease that was defined as disease with the largest dimension ≥ 7 cm. Stage distribution was IA in 33.3%, IIA in 39.1%, and IIB in 27.6%. Treatment was radiotherapy alone in 60 (69%) patients, chemotherapy and radiation in 23 (26.4%), and chemotherapy alone in 4 (4.6%). Results: The 10- and 20-year actuarial overall survival rates for all patients were 74.6% and 55.3%, and the corresponding disease-free survival rates were 72.4% and 67.5%, respectively. On univariate analysis, age > 40 years, B symptoms, nodular sclerosis or mixed cellularity histology, and decreased albumin or hemoglobin levels were statistically significant adverse pretreatment factors for overall survival. B symptoms, decreased albumin level, more than 3 sites of disease at presentation, and Stage II were statistically significant negative pretreatment prognostic factors for disease-free survival. Only B symptoms and decreased albumin level predicted worse outcome in both overall and disease-free survivals. On multivariate analysis, age > 40 years, nodular sclerosis and mixed cellularity histology, and decreased hemoglobin levels were three independent risk factors for overall survival. An analysis of the pattern of failure revealed that the majority of the patients with central Stage II disease who did not receive mantle radiation failed in the supradiaphragmatic area. Late complications of radiation were infrequent. Conclusions: Long-term follow-up of this group of patients revealed similar overall and disease-free long-term survival, as would be expected from supradiaphragmatic Hodgkin's disease. For patients with central Stage II disease, it is anticipated that supradiaphragmatic radiation therapy would improve the disease-free survival

[en] Purpose: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo). Methods and Materials: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or ≥ 40 Gy and (b) relapse patterns. Results: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of ≥ 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site. Conclusion: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients

[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: We analyzed in-field (IF) control in adults with early-stage Hodgkin's disease who received chemotherapy followed by radiotherapy (RT) in terms of the (1) chemotherapeutic regimen used and number of cycles delivered, (2) response to chemotherapy, and (3) initial tumor size. Cardiac toxicity and second malignancies, particularly the incidence of solid tumors in terms of the RT field size treated, were also examined. Methods and Materials: From 1980 to 1995, 286 patients ranging in age from 16 to 88 years (median: 28 years) with Ann Arbor clinical Stage I or II Hodgkin's disease underwent chemotherapy followed 3 to 4 weeks later by RT. There were 516 nodal sites measuring 0.5 to 19.0 cm at the start of chemotherapy, including 134 cases of bulky mediastinal disease. NOVP, MOPP, ABVD, CVPP/ABDIC, and other chemotherapeutic regimens were given to 161, 67, 19, 18, and 21 patients, respectively. Patients received 1-8 (median: 3) cycles of induction chemotherapy. All 533 gross nodal and extranodal sites of disease were included in the RT fields. The median prescribed RT dose for gross disease was 40.0 Gy given in 20 daily 2.0-Gy fractions. There was little variation in the RT dose. Eighty-five patients were treated with involved-field or regional RT (to one side of the diaphragm), and 201 patients were treated with extended-field RT (to both sides of the diaphragm), based on the protocol on which they were enrolled. Results: Follow-up of surviving patients ranged from 1.3 to 19.9 years (median: 7.4 years). Based on a review of simulation films, there were 16 IF, 8 marginal, and 15 out-of-field recurrences. The chemotherapeutic regimen used and the number of cycles of chemotherapy delivered did not significantly affect IF control. IF control also did not significantly depend on the response to induction chemotherapy. In cases where there was a confirmed or unconfirmed complete response as opposed to a partial response or stable disease in response to induction chemotherapy for bulky nodal disease, the 5-year IF control rates were 99% and 92%, respectively (p=0.0006). The 15-year actuarial risks of coronary artery disease requiring surgical intervention and of solid tumors were 4.1% and 16.8%, respectively. There was a trend toward a greater risk of solid tumors in patients who received extended-field RT rather than involved-field or regional RT (p=0.08). Conclusions: In patients with nonbulky disease, induction chemotherapy followed by RT to a median dose of 40.0 Gy resulted in excellent IF control, regardless of the chemotherapeutic regimen used, the fact that only 1-2 cycles of chemotherapy were delivered, and the response to chemotherapy. There was a trend toward a higher incidence of solid tumors in patients who received consolidation RT to both sides rather than only one side of the diaphragm. Ongoing Phase III trials will help clarify whether lower RT doses and smaller RT fields after chemotherapy can maintain the IF control seen in our study, but with a lower incidence of late complications in patients with Stage I or II Hodgkin's disease

[en] Purpose: At a time both when late complications and second malignancies have become a growing concern and when staging laparotomy has been largely abandoned and comparative studies for staging Hodgkin's disease by state of the art computed tomography (CT) vs. lymphangiography have revealed minimal differences in results for these procedures, our purpose for undertaking this study was twofold. Our initial reason was to determine and compare probabilities for negative abdominal findings for patients with Stage I presentations with those for patients with Stage II as determined by lymphangiography and subsequently by laparotomy for those patients who had negative lymphangiograms. Our second reason, being an extension of the first, was to create a resource that can be used in conjunction with other information for arriving at appropriate treatment decisions including giving either more or particularly less than standard institutional therapy and especially with respect to the abdomen. Methods and Materials: Data on 714 patients with prelymphangiogram Stage I-II upper torso presentations of Hodgkin's disease were entered prospectively in our database between 1968 and 1987. Twenty-eight with lymphocyte predominant disease, who had both negative lymphangiogram and negative laparotomy findings and 17 with questionable diagnoses of lymphocyte-depleted or unclassified disease were excluded from subsequent analyses of 669 patients with nodular sclerosis (NS) and mixed cellularity (MC) diagnoses. Results: Stage I: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms and nodular sclerosis histology, whereas negative laparotomy findings correlated strongly with a combination of no constitutional symptoms and female sex. Predicted probabilities depended on the ratios of favorable to unfavorable characteristics. Stage II: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms, nodular sclerosis histology, age < 40 years, and <4 involved sites, whereas negative laparotomy findings correlated strongly with a combination of <4 involved sites and mediastinal disease. Predicted probabilities again depended on the ratios of favorable to unfavorable characteristics. Conclusion: This study demonstrated that probabilities for negative abdominal findings for patients with supradiaphragmatic presentations of NS and MC Hodgkin's disease depended on: 1) whether the disease presented as Stage I or as Stage II; 2) whether staging was limited to a lymphangiogram or whether it included a laparotomy; and 3) or whether the clinical features associated with the presenting stage and methods of staging were favorable or unfavorable

[en] Purpose: Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Methods and Materials: We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ"2 test and logistic multivariate regression. Results: Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V_2_0 of >30%, V_1_5 of >35%, V_1_0 of >40%, and V_5 of >55%. The likelihood ratio χ"2 value was highest for V_5 >55% (χ"2 = 19.37). Conclusions: In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed or refractory lymphoma who received salvage chemotherapy and hematopoietic stem cell transplantation were at higher risk for symptomatic RP

[en] Purpose: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). Methods and Materials: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. Results: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET−) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET− versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET− vs 52% PET+ [P=.012], OS 78% for PET− and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET− vs 81% PET+ [P=.88]; OS 90% PET− vs 81% PET+ [P=.39]). Conclusion: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings