Early Stage Hodgkin's Disease Research Articles

Long-term complications of treatment and causes of mortality after Hodgkin's disease

The majority of newly diagnosed patients are expected to survive Hodgkin's disease because of effective therapies established during past 30 years. Long-term observations from large populations of treated patients have disclosed a variety of late effects of the disease and its therapy have contributed morbidity and excess mortality to Hodgkin's disease survivors. Secondary cancers have continued to accrue, and the risk relative to the general population has increased to 6.4 (95% confidence intervals: 5.5 to 7.3) in updated experience at Stanford University. Risks are significantly elevated for leukemia (primarily after chemotherapy regimens containing alkylating agents); non-Hodgkin's lymphoma; and tumors of the lung, breast, soft tissues, bone, stomach, pancreas, salivary gland, thyroid, and cutaneous melanoma. Early cardiovascular disease has also been observed and numerically exceeds second cancers as a cause of death in patients with early stage Hodgkin's disease (49 v 47 cases). Pulmonary dysfunction, thyroid dysfunction, infertility, psychosocial changes, gastrointestinal problems, soft-tissue changes, alterations in immunity, and risks for infection have also affected some treated patients. As these problems have been recognized, treatment approaches have been modified over the last 10 to 15 years, and early data suggest a decrease in some treatment sequellae.

Limited radiation therapy for selected patients with pathological stages IA and IIA Hodgkin's disease

The first definitive reports that early stage Hodgkin's disease (HD) could be cured by radiotherapy were published by Vera Peters in 1950 and by Easson and Russell in 1963. Since then, advances in understanding the natural history, refining the histopathologic classification, and development of a staging system have improved the management of HD. Several studies of early stage HD show greater than 80% actuarial 10- to 15-year freedom from relapse, and less than a 10% mortality from HD after treatment with radiation therapy alone. Radiotherapy has become so successful in the treatment of early stage HD (with combination chemotherapy reserved for relapse) that the risk of dying from other causes approaches the risk of dying from HD itself at 15 to 20 years following treatment. This article outlines the principles of treatment for favorable prognosis clinical stages IA and IIA HD, with emphasis on identifying patients with favorable features who may be treated effectively with mantle irradiation only.

Staging Laparotomy in the Management of Hodgkin's Disease: Is it Still Necessary?

Approximately 3,500 cases of stage I and II Hodgkin's disease are diagnosed each year in the United States. Traditionally, those patients who are considered candidates for primary radiation therapy undergo staging laparotomy (pathologic staging) to rule out definitively the presence of occult subdiaphragmatic disease. An appreciation of the risks of laparotomy and a recognition of the effectiveness of salvage chemotherapy in patients who fail primary radiation therapy have permitted the increased use of clinical staging as the basis for treatment of these patients. This article summarizes the literature regarding the need for staging laparotomy in early stage Hodgkin's disease and suggests alternative approaches to the management of these patients based on clinical criteria and prognostic factors.

795 Early stage Hodgkin's disease (HD): An analysis of prognostic factors in a large series from a single institution

Considerable progresses have been made in the treatment of HD in the last 25 years: cause specific survival rate for HD patients (pts) treated in Florence (all stages combined) is much higher for those treated after 1970 then in those treated before (74% vs 46% at 20 years). Results are even better for early stage HD. However, the analysis of prognostic factors in early stage HD is crucial to the definition of "high risk" groups, to be treated more aggressively, and of "low risk" subsets of patients, for whom the "therapeutic burden" could be reduced, to avoid long term sequelae. We present the results of an analysis on 841 Clinical Stage I–II HD pts (472 of whom have been submitted to staging laparotomy) consecutively treated 1960 through 1991, at the Florence Radiotherapy Department. Data from a single Institution are more homogeneous; moreover, our cases have been submitted to unlimited follow up and long term results have therefore a sound basis. Twenty-years cause specific survival rates are higher in patients: without "B" symptoms (77% vs 59%); with favourable histology (PL, NS); in the younger ones; in the females (78% vs 70%); in patients with CS I (84% vs 71%); in patients without lung hilar involvement (76% vs 65%); in patients presenting with high neck or subdiaphragmatic involvement only. Conversely, bulky mediastinal disease does not seem to adversely affect prognosis. The use of more aggressive treatment options (including chemotherapy) seems to ameliorate prognosis in patients with "B" symptoms. Results of uni- and multivariate analysis of the different factors affecting cause specific and relapse free survival will be discussed.

Pelvic relapse following subtotal lymphoid irradiation in early stage Hodgkin's disease—An analysis of risk, management, and outcome

To evaluate the time of onset, method of identification, management, and outcome of pelvic relapse following subtotal lymphoid irradiation (STLI) alone (mantle and paraaortic/spleen or splenic pedicle fields, excluding the pelvis) in supradiaphragmatic Stage I-II Hodgkin's disease. A retrospective analysis was performed of the initial, relapse, and regular follow-up evaluations of patients with pelvic relapse following STLI alone from 1968 to the present for supradiaphragmatic Stage I-II Hodgkin's disease after pathologic staging (PS-laparotomy staging) and clinical staging (CS-no laparotomy staging). Following staging, which included bipedal lymphangiography, 482 patients (408 PS and 74 CS), were treated with STLI alone for supradiaphragmatic Stage I-II Hodgkin's disease. The actuarial freedom from relapse at 20 years was 75% in PS patients and 81% in CS patients. The actuarial pelvic failure at 20 years was 7% for PS patients and 3% for CS patients. Of the 29 patients with pelvic relapse, 97% (28 of 29) occurred within 5 years of treatment, including 1 patient who progressed during initial treatment. Pelvic relapse was most commonly initially identified by abnormalities involving patient symptoms (62%), physical examination (55%), erythrocyte sedimentation rate (48%), and bipedal lymphangiogram and/or abdominal radiograph (38%). Relapse was limited to previously unirradiated sites in 17 patients (58%). In addition to pelvic lymph node disease, 3 patients (10%) had involvement of bone, and 4 patients (14%) had bone marrow involvement. Following relapse, all patients were treated with chemotherapy (MOP[P], MOP[P]/ABV[D], ABVD, or PAVe) and 19 of 29 patients received involved field consolidative irradiation. Twenty-one of 29 (72%) remained relapse free at the time of last follow-up evaluation, including 15 of 19 (79%) treated with combined therapy. Eight patients experienced a second relapse despite salvage therapy, and all eight expired with recurrent Hodgkin's disease. Two patients died of complications related to prior treatment. Therefore, the actuarial risk of death at 20 years associated with pelvic failure in the entire cohort of 482 patients was 2%. Pelvic relapse occurred in 7% of patients following STLI alone and was effectively diagnosed by regular follow-up, which included a combination of patient history, physical examination, and radiographic laboratory evaluation. Seventy-two percent of patients remained relapse free following salvage treatment, which included chemotherapy, resulting in an overall survival rate associated with pelvic control of 98%. This approach, therefore, spared the majority of patients the long-term risks associated with pelvic irradiation and/or chemotherapy, such as infertility, but maintained an excellent prognosis.

Results of a randomized study of early stage Hodgkin's disease using ABVD, EBVD, or MBVD

From January 1986 to December 1989, 157 previously untreated patients, with Hodgkin's disease stage I or II without bulky disease, were enrolled in a clinical comparative study. The objectives of the study were to compare the efficacy and safety of using epirubicine or mitoxantrone instead of adriamycin in the combination chemotherapy regimen ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The complete response rate was better in the patients treated with the ABVD or EBVD regimens compared to the MBVD arm. Also, differences in overall survival and relapse-free survival were better in the patients who received ABVD or EBVD compared to the MBVD regimen. Hematological, gastrointestinal and cardiac toxicity were similar in the three groups. Dose intensity, delays and complications were also similar in the three groups. The mitoxantrone-containing regimen was found to have less efficacy in comparison to the other regimens tested in the present study in patients with favorable stage I or II Hodgkin's disease.

Radiation therapy for early stage Hodgkin's disease: Australasian patterns of care

Analysis of treatment outcome for Stage I-IIA supradiaphragmatic Hodgkin's disease treated solely by irradiation in Australia and New Zealand. Patients with supradiaphragmatic Hodgkin's disease only who were treated by irradiation alone with curative intent between 1969 to 1988 were retrospectively reviewed. Ten radiation oncology departments in Australia and New Zealand contributed patient data to the study. Patient, tumor, and treatment variables were recorded. Disease-free interval, survival, and complications were analyzed. Eight hundred and twenty patients were reviewed. The median age was 29 years. There were 437 men and 383 women. The distribution of 310 clinically staged patients was 170 stage IA, 5 IB, and 135 IIA. Five hundred and ten patients received laparotomies, and pathologic staging was as follows: IA 214, IB 13, IIA 283. The 10-year actuarial disease-free rate was 69% and overall survival rate was 79%. Increasing age, male sex, higher number of involved sites, the use of involved field irradiation, no staging laparotomy, and earlier year of treatment were significantly associated with an increased risk of relapse and lower survival. Actuarial 10-year survival following recurrence was 48%. Acute complications requiring interruption to treatment occurred in 46 patients (6%), but < 1% had their treatment permanently suspended. Actuarial complication rates at 10 years were: cardiac 2%, pulmonary 3% and thyroid 5%. There were 44 second malignancies including 10 non-Hodgkin's lymphomas, 3 leukemias, 7 lung, and 6 breast cancers. Mean delay to the development of a second cancer was 6 years. The 10-year actuarial rate of second malignancy was 5%. The Australasian experience of early stage Hodgkin's disease is consistent with the results in the published literature and confirms that irradiation produces a high cure rate with minimal toxicity.

145 Detection of relapse in early stage Hodgkin's disease: Role of routine follow up studies

145 Detection of relapse in early stage Hodgkin's disease: Role of routine follow up studies

144 Randomized trial with early stage Hodgkin's disease testing 30GY vs 40GY extended field radiotherapy alone

144 Randomized trial with early stage Hodgkin's disease testing 30GY vs 40GY extended field radiotherapy alone

Should poor risk patients with Hodgkin's disease be sorted out for intensive treatments?

Death remains a common event in patients with advanced stage Hodgkin's disease (HD) and also occurs in early stages. Identification of the population of HD patients who would best benefit from an intensification of the treatment is therefore necessary in both cases. A comparative review of prognostic criteria must be attempted through recent randomized trials using conventional treatment, independently of criteria used by the autologous bone-marrow transplant (ABMT) teams which rather aim to select relapsing patients. When freedom from progression (FFP) is considered in recent large series, the factors which most often predict for a high risk of failure are bulky mediastinum, B symptoms, stage in advanced HD and the number of nodal areas in early HD. However, prognostic data available to date cannot sort out any group of patients that would clearly require a high dose/potentially risky therapy. Because of the failure to identify consensual prognostic factors, the population considered till now for upfront intensification is restricted to a very small subgroup of patients with advanced disease (< to 5% of them), which makes the conduct of randomized trials very difficult within reasonable delays. The potential to identify and to clear part of the difficulties encountered with the prognostic analysis depends on the population studied: size of the data base, follow-up, disease stages, treatments given, outcome criteria selected. Finally, "sorted out" new patients with advanced and perhaps early stage HD may benefit from treatment intensification. As the initial selection characteristics are still poorly defined, a proposition is made to collect, eventually through the International Data Base for Hodgkin's Disease (IDHD) pertinent recent trials and to launch a survey. The results of the survey will be discussed at the Third International Symposium on Hodgkin's lymphoma in Köln (21-23 September 1995). Hazards of intensified regimens may be better quantified by then, so that newer more efficient strategies may be designed.

2039 Extension of radiotherapy (involved field vs subtotal nodal) after short-term chemotherapy in early-stage Hodgkin's disease (ESHD)

2039 Extension of radiotherapy (involved field vs subtotal nodal) after short-term chemotherapy in early-stage Hodgkin's disease (ESHD)

Radiotherapy alone for early stage Hodgkin's disease: A 16 year experience at the Royal Adelaide Hospital

The records of all patients with stage I and II Hodgkin's disease treated with radiotherapy alone at the Royal Adelaide Hospital between 1970 and 1986 were reviewed. The aim was to ensure the results were equivalent to the best reported series, particularly as treating such patients with chemotherapy alone has been shown to produce equivalent overall survival figures with improved relapse-free survival. There were 104 patients of whom 67 had undergone staging laparotomy. Fifty-seven patients were stage I and 47 stage II. Nine patients had B symptoms. Overall survival at 10 years was 83% with disease-specific survival being 86% and relapse-free survival 68%. These results compare favourably with those in the world literature. Multivariate analysis only revealed stage as an independent predictor of improved relapse-free survival. The use of radiotherapy for most patients with early stage Hodgkin's disease is continued at Royal Adelaide Hospital. However, careful selection criteria need to be applied to minimize the incidence of relapse after radiotherapy.

Clarification of entry criteria for the European Organization for Research and Treatment of Cancer H5-favorable trial of early-stage Hodgkin's disease.

Clarification of entry criteria for the European Organization for Research and Treatment of Cancer H5-favorable trial of early-stage Hodgkin's disease.

The role of prognostic factors in treatment selection for early-stage Hodgkin's disease.

To identify poor prognostic factors in early-stage Hodgkin's disease that predict a high rate of relapse after radiotherapy alone. A total of 153 patients with stages I and II supradiaphragmatic Hodgkin's disease, treated between 1964 and 1986 with either radiotherapy alone (120 patients) or combined modality therapy (33 patients), were studied retrospectively to determine factors affecting freedom from relapse and absolute survival. Median follow-up was 13 years. Clinical factors were assessed by the stepwise use of a stratified log-rank test and included maximum tumor dimension in any site (< or = 6 cm or > 6 cm), age (< or = 40 or > 40), presence or absence of B symptoms, pathologic and clinical stages (I or II), number of sites involved (< or = 4 or > 4), gender, histologic subtype, and large mediastinal mass (none, small [< or = 6 cm], large [> 6 cm]). The only factors independently predicting a high rate of relapse were tumor dimension (> 6 cm) and number of sites (> 4 sites). At 10 years, in patients with and without the two poor prognostic factors treated with radiotherapy alone, the freedom from relapse rates were 53% and 84% (p < .0001) and the absolute survival rates were 72% and 85% (p = .004), respectively. Combined modality therapy significantly improved freedom from relapse, but not absolute survival, in patients with one or both poor prognostic factors. Two poor prognostic factors were identified that were highly significant in predicting a high risk of relapse after radiotherapy alone. The addition of three cycles of chemotherapy to standard radiotherapy significantly reduced the relapse rate in high-risk patients.

Second solid tumors and leukemia after treatment for Hodgkin's disease: An analysis of 1121 patients from a single institution

Purpose : To define the risk of having a second malignant neoplasm (ST) in different subsets of Hodgkin's disease patients and possibly to identify potentially avoidable therapeutic behaviors, linked with an increased second tumor probability. Methods and Materials : Cumulative probability of having a ST has been calculated for the different clinical and therapeutic subgroups of a population of 1121 patients consecutively treated (1960–1988) for Hodgkin's disease. Age groups at diagnosis were as follows: <20 years, 18%; 2040, 48%; 41–60, 26%; >60, 8%. Initial treatment consisted of radiation alone (67%), combined modality treatment (24%), chemotherapy alone (9%). Treatment for relapse was also coded, and the occurrence of ST was related both to initial treatment (considering relapsed patients as censored at relapse) and to the “overall” treatment burden, without censoring at relapse. Results : An increased ST risk has been observed in patients older at HD diagnosis. Second tumors cumulative probability rates were significantly higher in patients initially treated with chemotherapy, especially when associated with subtotal or total nodal irradiation (relative risks of 3.1 and 4.1, p = .03 and .005, respectively, when compared to involved field radiotherapy alone). The same trend was observed for second solid tumors. Acute leukemia was more frequent in patients initially given chemotherapy alone or associated with radiotherapy ( p = .01), and in those treated with an increasing number of cycles ( p = .004). “Salvage” chemotherapy after radiation alone at presentation does not seem to be linked with an increased risk of leukemia. Conclusion : The 15-year cumulative ST probability (11%) should be evaluated in the context of the very good cure rates achieved for Hodgkin's disease. The use of chemotherapy, particularly when associated with subtotal or total nodal irradiation, entails an increased risk of second malignancies and might be inappropriate in early stage Hodgkin's disease patients.

Controversies in the management of early stage Hodgkin's disease [see comments

Controversies in the management of early stage Hodgkin's disease [see comments

Early-stage Hodgkin's disease: Long-term results with radiotherapy alone or combined radiotherapy and chemotherapy

Controversy still exists over the optimal management of early-stage Hodgkin's disease (HD); presentation features may have a different prognostic impact according to initial therapy, and long-term toxicity must be fully evaluated. This study included 164 patients with stage IA-IIA HD treated with radiotherapy (RT) alone or combined radio- and chemotherapy (CT) according to presenting features and their attendant prognostic significance. The RT group included 88 patients with favorable prognostic features; the combined modality group included 76 patients with one or more unfavorable features. In the RT group, 85% of patients received extended-mantle or STNI; in the combined modality group, RT consisted of mantle- (49%), extended mantle- (37%), and involved-field irradiation (14%); CT consisted of 6 cycles of MOPP before 1984; 3 cycles of ABVD were substituted for MOPP thereafter. Complete remission was obtained in 94% and 99% of patients of the RT and combined modality groups, respectively. The 10-year actuarial relapse-free survival (RFS) in the RT group was 62% and was influenced by stage (p = 0.04) and histology (p = 0.01); in the combined modality group, RFS was 88% and was influenced by the presence of bulky disease. Overall survival and tumor mortality between the therapy groups were comparable. RT-related toxicity consisted of mediastinal fibrosis (8 cases), myelitis (3), hypothyroidism (2); other long-term events included 2 cases of acute leukemia in the combined MOPP and RT group. Altogether, 8 of 20 patients who died were in their first complete remission. In stage IA-IIA HD, the combined modality therapy reduced the risk of relapse compared to radiation alone; long-term toxicity of RT was not negligible and relapses could occur late.

Radiotherapy in early stage Hodgkin's disease.

Ninety-nine patients with "standard risk" Stage IA-IIA Hodgkin's disease observed between January 1983 and December 1990, received radiotherapy only. The complete response rate was 98% (97/99). Twenty-one patients (21%) relapsed, 17 of whom (81%) obtained a second complete remission. The projected 9-year overall survival and disease-free survival were 95% and 78%, respectively. In this study our goals were to reduce the irradiation volumes, to decrease the number of splenectomies performed at diagnosis, and to utilize radiotherapy alone in these patients. We were able to reduce the irradiation volumes in over 50% and 80% of the patients with disease in the upper torso and subdiaphragm, respectively. Furthermore, this therapeutic approach permitted us to reduce the acute and long-term toxic effects related to splenectomy and combined modality treatment.

The effect of ABVD chemotherapy with and without mediastinal irradiation on pulmonary function and symptomsin early-stage Hodgkin's disease

The effect of ABVD chemotherapy with and without mediastinal irradiation on pulmonary function and symptomsin early-stage Hodgkin's disease

Preliminary results of the EORTC-GPMC controlled clinical trial H7 in early-stage Hodgkin's disease

In this phase III trial, 770 patients with clinical stage I-II Hodgkin's disease (HD) have been enrolled since November 1988. Preliminary results are given for the 605 (79%) patients who have completed their initial therapy. Patients were grouped according to 6 pretreatment prognostic characteristics. In the very favourable (VF) group, treatment consisted of mantle field alone. In the favourable (F) group, patients were randomized to either subtotal nodal irradiation (STNI), or 6 cycles of EBVP (epirubicin, bleomycin, vinblastine, prednisone) followed by involved-field irradiation (IF-RT). Unfavourable (U) patients were randomized to either 6 cycles of EBVP plus IF-RT, or to 6 cycles of MOPP/ABV hybrid plus IF-RT. Of the 35 VF patients, none have progressed during radiotherapy. Four patients relapsed and were salvaged. Three-year failure-free survival (FFS) was 82%; overall survival (OS) was 100%. Of the 254 F patients, 130 were treated with STNI and 124 with EBVP plus IF-RT. At 3 years, FFS rates were 81% (1 progression, 14 relapses) and 79% (5 progressions, 8 relapses), respectively. Corresponding OS rates were 99% and 100%. Of the 316 U patients, 160 received EBVP and 156 MOPP/ABV. At 3 years, FFS rates were 72% (18 progressions, 20 relapses) and 88% (7 progressions, 6 relapses), respectively (p < 0.001). Although OS rates were identical (92%), the entry in the U-EBVP arm was stopped in November 1992. We conclude that a treatment strategy based on prognostic factors allows the use of less aggressive treatment in favourable patients.(ABSTRACT TRUNCATED AT 250 WORDS)