Treatment of breast-cancer-related lymphedema with or without manual lymphatic drainage--a randomized study. Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients. Randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer. A randomized, controlled, parallel-group clinical trial comparing multilayer bandaging followed by hosiery versus hosiery alone in the treatment of patients with lymphedema of the limb. Randomized, comparative study of high-dose (with autologous bone marrow support) versus low-dose cyclophosphamide, cisplatin, and carmustine as consolidation to adjuvant cyclophosphamide, doxorubicin, and fluorouracil for patients with operable stage II or III breast cancer involving 10 or more axillary lymph nodes (CALGB Protocol 9082). Cancer and Leukemia Group B. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Childhood non-Hodgkin's lymphoma. The results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2).
A prospective randomized study was carried out to investigate whether the addition of manual lymphatic drainage (MLD) to the standard therapy could improve treatment outcome in women with lymphedema of the ipsilateral arm after breast cancer treatment. Forty-two patients were randomly assigned to receive standard therapy or standard therapy plus MLD 8 times in 2 weeks and training in self-massage. The standard therapy consisted of use of a compression garment, exercises and information about lymphedema and skin care. The efficacy of treatment was evaluated by reduction in lymphedema volume during treatment and by improvement in symptoms potentially related to lymphedema. The patients were followed-up for a total of 12 months. The study showed that both groups obtained a significant reduction in edema and that MLD did not contribute significantly to reduce edema volume. Lymphoma patients commonly experience declines in physical functioning and quality of life (QoL) that may be reversed with exercise training.
                We conducted a randomized controlled trial in Edmonton, Alberta, Canada, between 2005 and 2008 that stratified 122 lymphoma patients by major disease type and current treatment status and randomly assigned them to usual care (UC; n = 62) or 12 weeks of supervised aerobic exercise training (AET; n = 60). Our primary end point was patient-rated physical functioning assessed by the Trial Outcome Index-Anemia. Secondary end points were overall QoL, psychosocial functioning, cardiovascular fitness, and body composition.
                Follow-up assessment for our primary end point was 96% (117 of 122) at postintervention and 90% (110 of 122) at 6-month follow-up. Median adherence to the supervised exercise program was 92%. At postintervention, AET was superior to UC for patient-rated physical functioning (mean group difference, +9.0; 95% CI, 2.0 to 16.0; P = .012), overall QoL (P = .021), fatigue (P = .013), happiness (P = .004), depression (P = .005), general health (P < .001), cardiovascular fitness (P < .001), and lean body mass (P = .008). Change in peak cardiovascular fitness mediated the change in patient-rated physical functioning. AET did not interfere with chemotherapy completion rate or treatment response. At 6-month follow-up, AET was still borderline or significantly superior to UC for overall QoL (P = .054), happiness (P = .034), and depression (P = .009) without an increased risk of disease recurrence/progression.
                AET significantly improved important patient-rated outcomes and objective physical functioning in lymphoma patients without interfering with medical treatments or response. Exercise training to improve cardiovascular fitness should be considered in the management of lymphoma patients. A non-randomised phase II study suggested a therapeutic effect of hyperbaric oxygen (HBO) therapy on arm lymphoedema following adjuvant radiotherapy for early breast cancer, justifying further investigation in a randomised trial.
                Fifty-eight patients with ≥ 15% increase in arm volume after supraclavicular ± axillary radiotherapy (axillary surgery in 52/58 patients) were randomised in a 2:1 ratio to HBO (n=38) or to best standard care (n=20). The HBO group breathed 100% oxygen at 2.4 atmospheres absolute for 100 min on 30 occasions over 6 weeks. Primary endpoint was ipsilateral limb volume expressed as a percentage of contralateral limb volume. Secondary endpoints included fractional removal rate of radioisotopic tracer from the arm, extracellular water content, patient self-assessments and UK SF-36 Health Survey Questionnaire.
                Of 53/58 (91.4%) patients with baseline assessments, 46 had 12-month assessments (86.8%). Median volume of ipsilateral limb (relative to contralateral) at baseline was 133.5% (IQR 126.0-152.3%) in the control group, and 135.5% (IQR 126.5-146.0%) in the treatment group. Twelve months after baseline the median (IQR) volume of the ipsilateral limb was 131.2% (IQR 122.7-151.5%) in the control group and 133.5% (IQR 122.3-144.9%) in the treatment group. Results for the secondary endpoints were similar between randomised groups.
                No evidence has been found of a beneficial effect of HBO in the treatment of arm lymphoedema following primary surgery and adjuvant radiotherapy for early breast cancer.
                Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. Mantle cell lymphoma (MCL) is characterized by a poor prognosis with a low to moderate sensitivity to chemotherapy and a median survival of only 3 to 4 years. In an attempt to improve outcome, the German Low Grade Lymphoma Study Group (GLSG) initiated a randomized trial comparing the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab (R-CHOP) with CHOP alone as first-line therapy for advanced-stage MCL.
                One hundred twenty-two previously untreated patients with advanced-stage MCL were randomly assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62). Patients up to 65 years of age achieving a partial or complete remission underwent a second randomization to either myeloablative radiochemotherapy followed by autologous stem-cell transplantation or interferon alfa maintenance (IFNalpha). All patients older than 65 years received IFNalpha maintenance.
                R-CHOP was significantly superior to CHOP in terms of overall response rate (94% v 75%; P = .0054), complete remission rate (34% v 7%; P = .00024), and time to treatment failure (TTF; median, 21 v 14 months; P = .0131). No differences were observed for progression-free survival. Toxicity was acceptable, with no major differences between the two therapeutic groups.
                The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission. Continuous, hyperfractionated, accelerated radiotherapy (CHART) has shown promise of improved tumour control and reduced late morbidity in pilot studies and has now been tested in a multicentre randomised controlled clinical trial.
                Patients with squamous cell cancer in the main sites within the head and neck region with the general exception of early T1 N0 tumours were entered into the study by 11 centres. There was a 3:2 randomisation to either CHART, where a dose of 54 Gy was given in 36 fractions over 12 days, or to conventional therapy where 66 Gy was given in 33 fractions over 6.5 weeks. A total of 918 patients were included over a 5 year period from March 1990.
                ACUTE MORBIDITY: Acute radiation mucositis was more severe with CHART, occurred earlier but settled sooner and was in nearly all cases healed by 8 weeks in both arms. Skin reactions were less severe and settled more quickly in the CHART treated patients. TUMOUR CONTROL AND SURVIVAL: Life table analyses of loco-regional control, primary tumour control, nodal control, disease-free interval, freedom from metastasis and survival showed no evidence of differences between the two arms. In exploratory subgroup analyses there was evidence of a greater response to CHART in younger patients (P = 0.041) and poorly differentiated tumours appeared to fare better with conventional radiotherapy (P = 0.030). In the larynx there was evidence of a trend towards increasing benefit with more advanced T stage (P = 0.002). LATE TREATMENT RELATED MORBIDITY: Osteoradionecrosis occurred in 0.4% of patients after CHART and 1.4% of patients after conventional radiotherapy. The incidence of chondritis or cartilage necrosis was similar in both arms. Life table analysis showed evidence of reduced severity in a number of late morbidities in favour of CHART. These were most striking for skin telangiectasia, superficial and deep ulceration of the mucosa and laryngeal oedema.
                Similar local turnout control was achieved by CHART as compared with conventional radiotherapy despite the reduction in total dose from 66 to 54 Gy supporting the importance of repopulation as a cause of radiation failure. The effects seen in advanced laryngeal cancer and those related to histological differentiation need further study. Reduced late morbidity is a factor which together with patient preference should be considered in the decision as to the programme of radiotherapy to employ in the curative treatment of head and neck cancer. Multilayered, low stretch bandages (MLB) combined with exercises, skin care, and manual lymphatic drainage therapy are recommended as an intensive phase of treatment for lymphedema patients. The relative efficacy of each of the components of this comprehensive treatment program have not been determined. This study aimed to compare the effect of multilayer bandaging as an initial phase of lymphedema treatment followed by elastic hosiery versus hosiery alone.
                A randomized, controlled, parallel-group trial was undertaken in the setting of the Lymphedema Clinic, The Royal Marsden Hospital, London. Ninety women with unilateral lymphedema (of the upper or lower limbs) were enrolled in the study. The interventions consisted of 18 days of multilayer bandaging followed by elastic hosiery or hosiery alone, each for a total period of 24 weeks. The main outcome measure was the percentage reduction in excess limb volume.
                The reduction in limb volume by MLB followed by hosiery was approximately double that from hosiery alone and was sustained over the 24-week period. The mean overall percentage reduction at 24 weeks was 31% (n = 32) for MLB versus 15.8% (n = 46) for hosiery alone, for a mean difference of 15. 2% (95% confidence interval, 6.2-24.2) (P = 0.001).
                Multilayer bandaging as an initial phase of treatment for lymphedema patients, followed by hosiery, achieves greater and more sustained limb volume reduction than hosiery alone.
                Copyright 2000 American Cancer Society. The prognosis for patients with primary breast cancer involving multiple axillary lymph nodes is poor. Only about 30% of patients remain disease-free at 5 years from diagnosis despite surgery, conventional-dose chemotherapy, and radiation therapy. In nonrandomized studies, the use of high-dose chemotherapy as consolidation therapy after standard-dose induction chemotherapy has resulted in an apparent improvement in disease-free survival rates to over 70%. These results have prompted the National Cancer Institute to sponsor large-scale, multicenter, randomized comparative trials of this strategy. This Intergroup Study (Cancer and Leukemia Group B 9082, Southwest Oncology Group 9114, and National Cancer Institute of Canada MA13) compares two treatment strategies in women with primary breast cancer involving 10 or more axillary lymph nodes. Arms A and B are identical in the use of four cycles of conventional therapy with cyclophosphamide and doxorubicin and fluorouracil, radiation therapy, and tamoxifen. The only difference between the two arms is the dose intensity of the cyclophosphamide, cisplatin, and carmustine given following conventional adjuvant treatment. Arm A dictates bone marrow, peripheral blood stem cell, and hematopoietic growth factor support and frequently requires a prolonged hospital stay with high resource utilization. Arm B, with its less dose-intensive therapy, requires considerably less support to apply the treatment. Because of the high cost of this therapy and the requirement for technology-intensive support, there has been considerable interest in economic outcome assessments. In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab (R) improves the prognosis when combined with chemotherapy. The present study investigated R-maintenance after R-chemotherapy. Patients with recurring or refractory FL and MCL were randomized to 4 courses of fludarabine, cyclophosphamide, and mitoxantrone (FCM) alone or combined with R (R-FCM). Responding patients underwent a second randomization for R-maintenance comprising 2 further courses of 4-times-weekly doses of R after 3 and 9 months. The first randomization was stopped after 147 patients, when R-FCM revealed a significantly better outcome. All subsequent patients received R-FCM. Of the 176 patients who are currently evaluable (as of October 2005), 138 received R-FCM for remission induction. Response duration was significantly prolonged by R-maintenance after R-FCM, with the median not being reached in this evaluation versus an estimated median of 16 months (P = .001). This beneficial effect was also observed when analyzing FL (P = .035) and MCL (P = .049) separately. Hence, R-maintenance is effective after salvage with R-chemotherapy and significantly prolongs response duration in patients with recurring or refractory FL or MCL. Members of the Childrens Cancer Study Group treated 234 eligible patients in a randomized trial designed to study the relative effectiveness of two therapy programs for the treatment of childhood and adolescent non-Hodgkin's lymphoma. Two chemotherapeutic strategies were compared: a 4-drug regimen (COMP) and a 10-drug regimen (modified LSA2-L2). Failure-free survival for all patients was 60 per cent at 24 months. In patients with disseminated disease treatment success was influenced by both the histologic subtype of disease and the therapeutic regimen followed. The 10-drug program was more effective than the 4-drug program in patients with disseminated lymphoblastic disease (two-year failure-free survival rate, 76 vs. 26 per cent, respectively; P = 0.0002), whereas the 4-drug program was more effective than the 10-drug program in those with nonlymphoblastic disease (57 vs. 28 per cent, respectively, P = 0.008). The less toxic, more easily administered 4-drug regimen was as effective as the 10-drug regimen in patients with localized disease (89 vs. 84 per cent, respectively).
All three trials have their limitations and have yet to be replicated, so their results must be viewed with caution. There is a clear need for well-designed, randomised trials of the whole range of physical therapies if the best approach to managing lymphoedema is to be determined.