IIA Hodgkin's Disease Research Articles

Limited Radiation Therapy for Selected Patients With Pathological Stages IA and IIA Hodgkin's Disease.

The first definitive reports that early stages 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.

Long-term results of a prospective trial of mantle irradiation alone for early-stage Hodgkin's disease

To determine the long-term treatment outcome and late effects of mantle irradiation alone in selected patients with early-stage Hodgkin's disease. Between 1988 and 2000, 87 patients with pathologic stage (Ann Arbor) I-IIA or clinical stage IA Hodgkin's disease were entered on to a prospective trial of mantle irradiation alone. Patients with B symptoms, large mediastinal adenopathy, or subcarinal or hilar involvement were excluded. The median doses to the mantle field and mediastinum were 36 Gy (range 30.3-40) and 38.6 Gy (range 30.6-44), respectively. The actuarial freedom from treatment failure (FFTF) and overall survival (OS) rates were calculated using the Kaplan-Meier technique. The median follow-up was 107 months (range 23-192). Thirteen of 87 patients (15%) relapsed at a median of 30 months (range 5-62). The 5- and 10-year actuarial FFTF rates were 86% and 84.7%, respectively. All 13 patients who relapsed are alive without evidence of disease at a median of 84 months (range 30-156) post-salvage therapy. Five patients developed a second malignancy at a median of 93 months (range 27-131). The 10-year actuarial risk of a second malignancy was 4.5%. There have been two deaths to date, both due to second malignancies. The 10-year OS rate was 98.2%. In selected patients with early-stage Hodgkin's disease, mantle irradiation alone has an excellent long-term survival rate, comparing favorably with the previous standard treatment of extended-field radiation therapy and the current standard of combined modality therapy.

Combined-Modality Therapy Versus Radiotherapy Alone for Treatment of Early-Stage Hodgkin's Disease: Cure Balanced Against Complications

The treatment of early-stage Hodgkin's disease (HD) has evolved from radiotherapy alone (RT) to combined-modality therapy (CMT) because of concerns about late adverse effects from high-dose subtotal nodal irradiation (STNI). However, there is little information regarding the long-term results of CMT programs that substantially reduce the dose and extent of radiation. In addition, lowering the total radiation dose may reduce the complication rate without compromising cure. This retrospective study compares the long-term results of STNI with CMT using modestly reduced RT dose in the treatment of early-stage HD. Between 1982 and 2002, 111 patients with stage IA and IIA HD were treated definitively with RT (mean dose, 37.9 Gy); 70 patients were treated with CMT with low-dose involved-field radiotherapy (LDIFRT; mean dose, 25.5 Gy). Median follow-up was 11.7 years for RT patients and 8.1 years for the CMT group. There was a trend toward improved 20-year overall survival with CMT (83% v 70%; P = .405). No second cancers were observed in the CMT group; in the RT group the actuarial frequency of a second cancer was 16% at 20 years. There was no difference in the frequency of cardiac complications (9% v 6%, RT v CMT). In this retrospective review, CMT with LDIFRT was effective in curing early-stage HD and was not associated with an increase in second malignancies. For RT alone, a moderate dose seemed to reduce cardiac complications but did not lessen second malignancies compared with higher doses used historically.

ABVD Plus Subtotal Nodal Versus Involved-Field Radiotherapy in Early-Stage Hodgkin's Disease: Long-Term Results

Radiation therapy (RT) alone can cure more than 80% of all patients with pathologic stage IA, IB, and IIA Hodgkin's disease, but some prognostic factors unfavorably affect treatment outcome. Combined-modality approaches improved results compared with RT, but the optimal extent of RT fields when combined with chemotherapy warranted additional evaluation. In February 1990, we activated a prospective trial in patients with early, clinically staged Hodgkin's disease to assess efficacy and tolerability of four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by either subtotal nodal plus spleen irradiation (STNI) or involved-field radiotherapy (IFRT). Main patient characteristics were fairly well balanced between the two arms. Complete remission was achieved in 100% and in 97% of patients, respectively. The 12-year freedom from progression rates were 93% (95% CI, 83% to 100%) after ABVD and STNI, and 94% (95% CI, 88% to 100%) after ABVD and IFRT, whereas the figures for overall survival were 96% (95% CI, 91% to 100%) and 94% (95% CI, 89% to 100%), respectively. Apart from three patients who developed second malignancies in the STNI arm, treatment-related morbidities were mild. Present long-term findings suggest that, after four cycles of ABVD, IFRT can achieve a worthwhile outcome. The limited size of our patient sample, however, had no adequate statistical power to test for noninferiority of IFRT versus STNI. Despite this, ABVD followed by IFRT can be considered an effective and safe modality in early Hodgkin's disease with both favorable and unfavorable presentation.

Efficacy of Vinblastine, Bleomycin, Methotrexate (VBM) Combination Chemotherapy with Involved Field Radiotherapy in Early Stage (I-IIA) Hodgkin Disease Patients

Vinblastine, bleomycin, methotrexate (VBM) combination chemotherapy (CT) with involved field radiotherapy (IFRT) was first described by the Stanford group as an active regimen in early stage Hodgkin's disease (HD). Here, we report our retrospective experience of a modified VBM schedule + IFRT in a similar group of patients. From 1988,49 patients with stage I–IIA HD received vinblastine (VBL) 6 mg/m2, bleomycin (BLM) 101U/m2, methotrexate (MTX) 30 mg/m2 day 1,8 every four weeks for three cycles; IFRT was delivered four weeks later followed by three additional cycles of VBM with a dose reduction of BLM (61U/m2). The regimen was well tolerated, with grade 3–4 neutropenia occurring in 20 patients. No acute or late pulmonary toxicity was recorded in our series. Estimated Freedom from Progression (FFP) and Overall Survival (0s) at five years are 75% (95% C1, 60.1%–92.2%) and 85% (95% C1, 73.6%–98.1%), respectively.In this retrospective analysis, VBM + IFRT treatment with bleomycin dose reduction seems safe and active. Such combination could be considered as first line treatment for early stage HD patients with favorable prognosis and/or not suitable for anthracyclines-containing regimens.

CHEMO- AND RADIOSENSITIVITY TESTING IN A PATIENT WITH ATAXIA TELANGIECTASIA AND HODGKIN DISEASE

Treatment of Hodgkin disease (HD) in ataxia telangiectasia (AT) patients is hampered by hypersensitivity to radiation and chemotherapy. Most patients die, due to toxicity or, rarely, to progressive disease. The authors report on a 9-year-old girl with stage IIA HD and AT. She was treated with a tailored combined modality approach. No unacceptable toxicity was found, but the girl died of a relapse outside their radiation field. In comparison with fibroblasts of non-AT patients, the fibroblasts of the patient were 3 times as sensitive for radiotherapy but just 1.2 times as sensitive for doxorubicin. A good correlation was shown between in vitro radio- and chemosensitivity testing and the observed clinical toxicity. The authors suggest, therefore, treating AT patients as much as possible according to standard protocols by adjusting the radiotherapy delivery and the chemotherapy regimen to individual doses derived from in vitro radio- and chemosensitivity testing.

British National Lymphoma Investigation: Pilot Studies of Neoadjuvant Chemotherapy in Clinical Stage Ia and IIa Hodgkin's Disease

In order to improve treatment in early Stage IA and IIA Hodgkin's disease, the British National Lymphoma Investigation (BNLI) has evaluated two neoadjuvant chemotherapy regimens with involved field radiotherapy. This article reports the results of the methotrexate, vinblastine and prednisolone (MVP) study in 39 patients and updates the previous report on vinblastine, bleomycin and methotrexate (VBM) in 30 patients. Both studies recruited clinical Stage IA or IIA Hodgkin's disease patients with intermediate risk of relapse into a prospective multicentre Phase II study. They received two cycles of chemotherapy followed by involved field radiotherapy and then four further cycles of chemotherapy. For MVP the 5-year survival is 97% and for VBM it is 93%. The 5-year event-free survival rates are 71% and 87% respectively.The acute pulmonary and haematological toxicity occurring with VBM was not acceptable and therefore the MVP study was performed. There was less toxicity with this regimen although modest acute pulmonary toxicity was still observed. However, in view of the length of treatment with MVP (9 months) and the excellent results reported by the Manchester group, future efforts of the BNLI are to be directed towards a new short course chemotherapy regimen, VAPEC-B (vincristine, doxorubicin, prednisolone, etoposide, cyclophosphamide and bleomycin).

Long‐term results of 60 patients with pathologic stage I & IIA Hodgkin's disease treated with exclusive mantle radiation therapy

Between January 1972 and December 1982 60 patients with pathological stage IA and IIA Hodgkin's disease (HD) were submitted to Mantle irradiation only. Twenty-five were in stage I (32.1%) and 35 in stage II (67.9%). All patients were submitted to staging laparotomy. Cases with large mediastinal mass were excluded from this series. Delivered doses were 44 Gy in involved areas, 40 Gy on the mediastinum and 36 Gy on uninvolved sites. Twenty-four patients in stage I (96%) and 33 in stage II (94.2%) obtained complete remission. Actuarial 10- and 20-yr overall (OS) rates were 86% and 79.1%, respectively. Event-free (EFS) and relapse-free (RFS) survival rates at 10 and 20 yr were 67.5% and 62.1%, respectively. The occurrence of disease relapse resulted in the only statistical significant prognostic factor for OS in both univariate and multivariate analysis. Distant and extranodal recurrences were significantly (P<0.01) related to a reduced OS. On multivariate analysis stage was the only determinant factor for increased RFS. Extended field RT proved to be an effective curative modality for stage I HD patients, whereas 15 out of 33 patients in stage II relapsed requiring salvage therapy. Long-term analysis of survival and treatment-related morbidity rates will improve our knowledge and assist the physicians to choose the therapeutic option to offer to HD patients.

Pancreatic Cancer in a Young Adult After Treatment for Hodgkin's Disease

The authors present a case of adenocarcinoma of the head of the pancreas, which arose 14 years after extended field irradiation for Stage IIA Hodgkin's disease. The patient was aged 37 years at the time of the pancreatic cancer, which was situated within the previously irradiated volume.

Prognostic factors affecting disease-free survival in patients with Hodgkin's disease stages IA and IIA treated initially with radiotherapy alone in a single centre during 1973 to 1992

One hundred forty-nine patients with either stage IA (90 patients) or stage IIA (59 patients) Hodgkin's disease (HD) received radiotherapy alone as their first line treatment. Only stage of the nine factors selected for Cox multivariate analysis was of prognostic significance. Patients with grade 1 nodular sclerosing HD did not have a significantly better disease-free survival than those with grade 2 disease.

Occurrence of a myocardial infarction in a 31‐year‐old woman with severe hypercholesterolemia (type IIA hyperlipidemia) three years after mantle irradiation for stage IIA Hodgkin's disease

Occurrence of a myocardial infarction in a 31‐year‐old woman with severe hypercholesterolemia (type IIA hyperlipidemia) three years after mantle irradiation for stage IIA Hodgkin's disease

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.

Vinblastine, bleomycin, and methotrexate chemotherapy plus extended-field radiotherapy in early, favorably presenting, clinically staged Hodgkin's patients: the Gruppo Italiano per lo Studio dei Linfomi Experience.

To ascertain whether vinblastine, bleomycin, and methotrexate (VBM) (CT) combined with extended-field radiotherapy (EF RT) is effective enough to spare laparotomy in early, favorably presenting Hodgkin's disease (HD) patients. Fifty patients with clinical stage IA or IIA HD with favorable histology and no bulky masses entered a prospective multicenter study started in January 1988. The median follow-up time was 38 months. All patients achieved a complete remission (CR). Five relapsed after 3 to 40 months and underwent successful salvage therapy. The actuarial remission rate was 0.89% at 3 years and 0.82% at 5 years. Two patients died in CR: one of severe pulmonary toxicity, the other of a second neoplasia (adenocarcinoma of the lung), 2 and 43 months after the end of therapy, respectively. The hematologic toxicity recorded during VBM CT was mild on the whole. Major toxicity was represented by pulmonary side effects and neurologic symptoms. Multiple regression analysis demonstrated that pulmonary toxicity was significantly related only to the amount of RT delivered to the mediastinum and not to the relative dose of bleomycin, to the dose-intensities of the three drugs in the regimen, or to patient age or sex. The same statistical technique showed that the only clinical factor related to grade of neurotoxicity was vinblastine dosage. VBM CT combined with EF RT is an effective treatment for early, clinically staged, favorable HD patients. However, the toxicity of this combination suggests that certain modifications should be evaluated.

22 A prospective trial of mantle irradiation alone for selected patients with PS IA - IIA Hodgkin's disease

22 A prospective trial of mantle irradiation alone for selected patients with PS IA - IIA Hodgkin's disease

Mantle irradiation alone for selected patients with laparotomy-staged IA to IIA Hodgkin's disease: preliminary results of a prospective trial.

To determine the feasibility of omitting prophylactic paraaortic irradiation in selected patients with laparotomy-staged (pathologically staged [PS]) IA to IIA Hodgkin's disease. We initiated a prospective single-arm trial in October 1988 to study the role of mantle irradiation alone in selected PS IA to IIA patients with Hodgkin's disease. A total of 37 patients have been entered onto this trial. Entrance criteria included nodular sclerosis (NS) or lymphocyte predominance (LP) histology, absence of B symptoms, disease limited above the carina, and a negative laparotomy. Results of treatment of 23 patients in the prospective trial, monitored off treatment for > or = 1 year, are presented. Twenty-three additional PS IA to IIA patients, treated with mantle irradiation alone from 1970 to 1987, were analyzed as a comparison group. The median follow-up durations were 32 and 113 months, respectively, for the two groups. The 4-year actuarial rates of freedom from relapse and overall survival are 83% and 100%, respectively, for the prospective trial. The 10-year actuarial rates of freedom from relapse and overall survival are 83% and 89%, respectively, for retrospectively studied patients. There have been five recurrences among 46 patients who received mantle irradiation alone, all with a component of relapse below the diaphragm. These early results support the use of mantle irradiation alone in selected PS IA to IIA patients with NS or LP histology. Relapses, although rare, have occurred predominantly below the diaphragm. This suggests the need for continued long-term surveillance of abdominal and pelvic nodes in this group of treated patients.

Extended-field radiotherapy in favorable stage IA–IIA Hodgkin's disease (Prognostic role of stage)

Purpose : The study was undertaken to evaluate the long-term results in a favorable subset of patients with pathological Stage IA–IIA treated with irradiation alone. Methods and Materials : One hundred and forty-seven adults with laparotomy- Staged IA–IIA “favorable” Hodgkin's disease were treated with primary subtotal nodal irradiation. Patients with infradiaphragmatic presentation were irradiated through paraortic and inguino-iliac node chains (inverted Y field) followed by prophylactic mediastinal and supraclavicular fields. Results : Actuarial overall survival (OS) at 7 years (median follow-up 77 months) was: 93% for the whole series, 94% for Stage I, and 92% for Stage II. The freedom from first progression (FFP) (80% for the whole series) showed a statistically significant difference ( p = 0.008) between Stage I (88%) and Stage II (71%). By univariate analysis, stage alone had an independent prognostic significance for OS and FFP. Of the 29 relapsed patients, 8 were previously classified as Stage I and 21 as Stage II; 16 of 29 (55%) of the relapses occurred in the pelvis and 9 in extranodal sites. After salvage treatment with chemotherapy all patients achieved a second complete remission. Seven second malignancies (two acute nonlymphocytic leukemias, one preleukemic syndrome, and four solid tumors) have been detected so far. Hypothyroidism was observed in 16% of patients and a reversible pulmonary restrictive syndrome in 14% of cases, respectively. Conclusions : Within 7 years from radiation therapy, about one-quarter of the patients with Stage II disease will experience a relapse and need intensive salvage chemotherapy. This is not invariably successful and safe, for it may be complicated by either acute or potentially fatal long-term adverse effects, such as second malignancies and cardiac or pulmonary sequelae, in about 5% of patients. The high frequency of relapse in Stage IIA patients suggests a combined modality approach with relatively short-term chemotherapy not including alkylating agents.

Long-term results of curative irradiation in pathologically staged IA and IIA Hodgkin disease.

One hundred seventy-six patients with pathologically staged IA and IIA Hodgkin disease (HD) treated with irradiation alone were evaluated for long-term survival and freedom from relapse (FFR). Most of the patients received treatment to mantle and paraaortic fields; chemotherapy was not given except as salvage therapy. For pathologically staged IA disease, the 5-, 10-, and 15-year survival rates were 94%; the corresponding FFR rates were 96%, 93%, and 93%. For pathologically staged IIA disease, respective survival rates were 93%, 89%, and 80%, with FFR rates of 86%, 84%, and 84%. Twenty-one patients (12%) had relapse of HD; salvage therapy was successful in 11 of these patients. Pelvic recurrence was uncommon (three of 176 cases [2%]). No patient developed leukemia, and only two patients developed second malignancies (lung cancer in both cases). The authors conclude that radiation therapy is effective in treatment of early-stage HD.

Mantle irradiation alone for selected patients with pathologically staged (PS) Ia–IIa Hodgkin's disease: Preliminary results of a prospective trial

Mantle irradiation alone for selected patients with pathologically staged (PS) Ia–IIa Hodgkin's disease: Preliminary results of a prospective trial

Early stage Hodgkin's disease: Ten-year results of a non-randomised study with radiotherapy alone or combined with MOPP

From September 1976 to June 1982, 201 consecutive patients with stage I (A and B)-IIA Hodgkin's disease were stratified in two groups according to prognostic factors. The F group included 116 patients with favourable presentation: they were staged with laparotomy and treated with subtotal or total nodal radiotherapy alone. The U group included 85 cases with unfavourable presentation who were staged by laparoscopy and treated with 3MOPP (mechlorethamine, vincristine, procarbazine, prednisone)-radiotherapy-3MOPP. At 10 years the F group showed a freedom from progression (FFP) of 71%, with significant difference between stage I and II (85% vs. 59%; P=0.003) and an overall survival of 84%. The results of the U group were: FFP 83%, overall survival 74%, and the findings were not influenced by stage. FFP in patients with bulky vs. not bulky lymphoma was 70% vs. 87% ( P=0.04). No secondary acute non-lymphocytic leukaemia developed among patients treated with radiotherapy and in continuous complete remission, while acute leukaemia occurred in the F group patients who received salvage chemotherapy (4 of 31 cases) and in the U group (3 of 85 cases). Present results confirm the usefulness of radiotherapy alone in favourable pathological stage IA. All other disease stages will require a different strategy that should consist of radiotherapy combined with short-term effective regimens, such as ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or VBM (vinblastine, bleomycin and methotrexate) to reduce the incidence of MOPP-associated gonadal dysfunction and leukaemogenesis.

Use of the Internal Mammary Artery for Myocardial Revascularization in a Patient With Radiation-Induced Coronary Artery Disease

A 9-year-old boy with clinical stage IIA Hodgkin's disease underwent radiotherapy to the neck and mediastinum. Twenty-two years later, he sought medical attention because of angina pectoris. Cardiac catheterization revealed proximally located high-grade stenoses of the left main, left anterior descending, circumflex, and right coronary arteries. He underwent coronary artery bypass grafting with use of the left internal mammary artery to the left anterior descending coronary artery and reversed saphenous vein grafts to the circumflex and right coronary arteries. The postoperative course was uncomplicated. Previous radiotherapy to the mediastinum should be considered a risk factor for the development of premature coronary artery disease. Surgical revascularization is the preferred method of management. A combination of an internal mammary artery graft and a saphenous vein graft should be used in young patients.