The Case for Chemotherapy Alone for Limited-Stage Hodgkin's Lymphoma

The Hodgkin''s Disease.6 study is critically examined, and the question of whether or not radiation should be used at all in the treatment of patients with limited-stage Hodgkin''s lymphoma is argued to be more relevant than what type of radiation to use, given the remarkably good outcome with chemotherapy alone.     

The evolution and summary results of the Stanford randomized clinical trials of the management of Hodgkin's disease: 1962-1984

This is a summary report of the Stanford randomized clinical trials of the management of Hodgkin's disease, initiated in 1962. There have been four major changes in the treatment protocols during this 22 year period. Between 1962-67, 132 patients with CS I, II and III disease were enrolled on various radiation trials. Between 1968-74, 367 patients were enrolled on studies primarily evaluating the role of adjuvant MOPP chemotherapy. Between 1974-80, variations in the chemotherapy regimen and the sequences of the combined modality programs were studied. The current studies, initiated in 1980, have enrolled 102 patients, and test a new mild adjuvant chemotherapy, VBM, (vinblastine, bleomycin and methotrexate) and utilizes ABVD in combined modality and alternating regimens. During the two decades of these studies, involving more than 800 patients, the initial remission rate and duration and the survival of all patients treated have progressively improved.     

Combined modality therapy for early Hodgkin's disease: Heterogeneity in Australasian clinical practice

Two case studies of locally extensive clinical stage IIA Hodgkin's disease (HD) were presented to radiation oncologists at a meeting of the Australasian Radiation Oncology Lymphoma Group, and subsequently to non-attending members who were asked to indicate their recommended treatment. This paper discusses the 25 responses which were notable by considerable heterogeneity in philosophy and detail. There is clearly no consensus among Australasian radiation oncologists at present, although combined modality therapy (CMT) with Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by low-medium-dose involved field radiotherapy (25–36 Gy) was the most popular response. The literature on radiation dose and chemotherapy in CMT for HD is then reviewed. It seems very likely that low doses in the range of 25–30 Gy (at 1.5–2.0 Gy per fraction) are sufficient. The ABVD should be considered as the ‘standard’ regimen at present, although the optimal sequencing with radiation and number of cycles remain unknown. The heterogeneity of responses to management of the case studies raises questions about ongoing education processes in radiation and medical oncology. Hypothetical case management review may complement currently proposed methods of assessing continuing medical education.     

MOPP chemotherapy plus irradiation for Hodgkin's disease, stages IA to IIIB. Long-term results of the prospective trial H72 (1972-1976, 334 patients)

From April 1972 to December 1976, 334 patients with Hodgkin's disease, CS IA-IIIB, were prospectively treated with combined chemotherapy and radiation. The 166 stages IA and II2A were clinically staged only; the 168 other patients were randomized to clinical or pathological staging. All patients received 3 or 6 cycles of MOPP followed by Mantle field with or without mediastinal irradiation and/or inverted Y or lumbo-aortic field according to initial stage, presentation and protocol. At completion of therapy, 317 patients were in complete remission. Twenty-six patients relapsed and 43 died including 5 with leukemia and 6 with infection. Overall 12-year survival and relapse-free rates are 86.6 +/- 3.08 per cent and 91.5 +/- 3.2 per cent respectively (IA: 95.3 and 95.3 per cent; IIA: 87.8 and 92.1 per cent; IIIA: 83.3 and 100 per cent; IB, IIB: 81.7 and 89.2 per cent; IIIB: 67.8 and 73.7 per cent). The randomized comparison between clinical staging plus 6 cycles of MOPP and laparotomy staging plus 3 cycles of MOPP in final stage II3+A, IB, IIB patients showed no significant 12-year survival differences (90.8 versus 85.6 per cent). With this combined modality treatment policy, high survival rates are obtained using only 3 cycles of MOPP and radiotherapy in CS IA, II2A and in PS II3+, IB, IIB. Laparotomy staging may be unnecessary if 6 cycles of MOPP are employed before irradiation in CS IIA, IB, IIB disease and if 3 cycles of MOPP are followed by irradiation in CSIA and II2A disease. Mediastinal irradiation can be avoided in patients with supradiaphragmatic disease without mediastinal involvement.     

The management of stage 111a hodgkin's disease

Forty patients with pathological Stage IIIA Hodgkin's disease were allocated to receive either total nodal irradiation (TNI) or 6 cycles of chemotherapy with Nitrogen Mustard (Mustine), Vinblastine, Procarbazine and Prednisolone (MVPP) as initial treatment. The complete remission rate for both groups was 100%, with 5-year actuarial disease-free survival figures of 74 and 87% for TNI and MVPP respectively (median duration of follow-up = 48 months). Eighty-eight per cent of TNI treated patients were alive at 5 years compared with 100% in the MVPP group. Three patients died, two who were treated with TNI and one who received MVPP. Treatment related morbidity included one patient with osteonecrosis and one with a second malignancy. Given the length of follow-up available, these results demonstrate no significant difference between TNI and MVPP for patients with Stage IIIA disease; it is unlikely that further patient entry into this particular study will allow any conclusion to be reached regarding the optimal form of management. We would recommend that individual disease characteristics within Stage IIIA be used as a basis for future treatment decisions with the understanding that further information regarding morbidity may become available with prolonged follow-up.     

First Reported Case of Disease: Peliosis Hepatis as Cardinal Symptom of Hodgkin's Lymphoma

We present the case of a 25‐year‐old woman with a history of weakness, weight loss, anemia, and elevated liver enzymes. Outpatient diagnostic evaluation, including abdominal ultrasound and endoscopies, revealed no conclusive explanation for the clinical picture and the patient was admitted to our clinic. Because of the hepatosplenomegaly together with the elevated liver enzymes, one of our differential diagnoses was that of liver disease. To clarify this, we performed a minilaparoscopy, which showed multiple diffuse distributed spots of livid color without clear margins distributed all over both liver lobes. A biopsy taken from these areas revealed the diagnosis of peliosis hepatis with irregular and diffusely enlarged hepatic sinusoids with an irregular structure. Peliosis hepatis is associated with numerous infectious and neoplastic diseases, but also occurs as a result of toxic liver damage. Further evaluation of our patient with an x‐ray and a computed tomography (CT) scan revealed a mediastinal mass and a CT‐guided biopsy showed classical Hodgkin's lymphoma. After completing further screening, a definitive diagnosis of Hodgkin's lymphoma stage II/N/B (Ann‐Arbor) was established and chemotherapy according to the German Hodgkin's study group protocol with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (the BEACOPP regimen) was initiated. After the first chemotherapy cycle, the patient's symptoms and laboratory values improved rapidly. Taken together, we present the case of a patient with peliosis hepatis as an uncommon manifestation of Hodgkin's lymphoma. Despite an extensive literature search, we could not find any case of peliosis hepatis associated with a de novo diagnosis of classical Hodgkin's disease.     

Radiotherapy for Hodgkin's disease in pregnancy

Hodgkin's disease diagnosed during pregnancy poses a dilemma as there are risks of abortion and fetal malformation with the use of radiotherapy and chemotherapy. A patient with Hodgkin's disease during pregnancy treated with radiotherapy is presented.     

Reduction of the treated volume to involved node radiation therapy as part of combined modality treatment for early stage aggressive non-Hodgkin’s lymphoma

Background and purpose

This retrospective study investigated whether focused involved node radiation therapy (INRT) can safely replace involved field RT (IFRT) in patients with early stage aggressive NHL.

Patients and methods

We included 258 patients with stage I/II aggressive NHL who received combined modality treatment (87%) or primary RT alone (13%). RT consisted of a total dose of 30–40 Gy in 15–20 fractions IFRT or INRT. We compared survival, relapse pattern, radiation-related toxicity and quality of life for both RT techniques.

Results

Type of RT was not related to the outcome in either the uni- or multivariate survival analysis. Relapses developed in 59 of 252 patients (23%) of which 47 (80%) were documented as distant recurrence only. Failure of the INRT technique was noted in one patient. There was no significant difference in acute radiation-related toxicity between RT-groups but IFRT showed a significantly higher incidence of higher grade toxicities. Patients treated with INRT had a significantly better physical functioning and global quality of life compared to the IFRT group.

Conclusions

Given the retrospective nature of this study, no solid conclusions can be drawn. However, in view of the equivalent efficacy and more favorable toxicity profile, the replacement of IFRT by INRT in combination with chemo-(immuno)-therapy looks very attractive for patients with early stage aggressive NHL.     

Hodgkin's disease: combination chemotherapy for relapse following radical radiotherapy.

The results of Mustine, Vinblastine, Procarbazine, Prednisolone (MVPP) combination chemotherapy for relapsed Hodgkin's disease in 33 patients who were treated initially by definitive radiotherapy are analyzed. Twenty three of 27 (85%) who received chemotherapy at first relapse achieved complete remission (CR); 20 of these remained in remission at periods of 13–96 months (median 53 months) from treatment. Six patients were retreated by irradiation at first recurrence and all suffered further relapse within 14 months. Only 3 (50%) of this group achieved CR with subsequent chemotherapy. The results of radiotherapy for early stage Hodgkin's disease are improving now that certain presentations that are associated with high risk for relapse when treated by irradiation alone are recognized. The high CR rate obtained with MVPP in patients with recurrence following radiotherapy suggests that chemotherapy may reasonably be withheld in the initial management of localized disease, thus reducing the risk of iatrogenic complications associated with combined modality therapy.     

Dynamic dose-shaping by gravity-oriented absorbers for total lymph node irradiation

Rotational therapy with gravity-oriented absorbers is proposed for better total lymph node irradiation (TLI). Two metal semicylinders are joined coaxially (face to face) to form a radiation absorber that is centrally suspended in the beam. During rotation this absorber is kept parallel to itself by gravity, like the riders of a Ferris wheel. The vertebrae remain continuously protected under the absorber's “shadow”. The circular full-dose region, achieved by ordinary rotation, is now transformed into a “horse-shoe” region embracing the spine anteriorly. The abdominal lymph nodes are thus irradiated while the spine and most of the normal tissue around the spine are protected. A similar technique is applied for the selective irradiation of the pelvic lymph nodes, which are confined in the two legs of an inverted V region.     

Treatment selection for stage IIIA Hodgkin's disease patients

Two treatment policies for the therapy of patients with Stage IIIA Hodgkin's disease are compared. From 1969-1976, 49 newly diagnosed and pathologically staged IIIA patients received total nodal irradiation (TNI) alone (no liver irradiation). Although actuarial survival was 80% at 5 years and 68% at 10 years, actuarial freedom from relapse was only 38% at 5 years. Accordingly, a new treatment policy was instituted in 1976. Patients with either CS IIIA disease, multiple splenic nodules, IIIA with a large mediastinal mass or III2, received combined modality therapy (combination chemotherapy and irradiation). All others received TNI. Thirty-six patients have been treated under the new program. The actuarial survival is 90% at 5 years and the relapse-free survival is 87%, suggesting the superiority of this approach.     

Bulky mediastinal Hodgkin's disease management and prognosis

Of a total of 235 Stage I and II Hodgkin's disease patients treated between 1970 and 1979, 103 (43.8 per cent) had mediastinal involvement in 45 of whom the disease was bulky and in 58 non-bulky. This report concentrates on bulky disease patients of whom 45 per cent did not relapse after therapy and 71 per cent are alive. Patients with mediastinal disease were treated with radiotherapy (63), sequential chemo-radiotherapy (37) or chemotherapy alone (3). In the radiotherapy group the relapse rate for bulky disease was significantly higher (65 per cent) than for non-bulky disease (44 per cent) (P less than 0.05) although there was no significant difference in survival. Neither relapse rate nor survival differed significantly in bulky disease patients treated with radiotherapy compared with combined chemo-radiotherapy although there was a 20 per cent difference in relapse-free survival rate in favour of the combined treatment group at five years. Treatments were not allocated randomly and the chemo-radiotherapy group contained a disproportionate number of patients with adverse features (greater than 3 node areas involved, limited lung extension) compared with the irradiated group; 11/25 and 2/17 respectively. The number of lymph node areas involved appeared to influence the relapse rate in the radiotherapy group. There was no correlation between mediastinal mass size and number of node areas involved suggesting that these two features may be independent prognostic factors.     

Potential Benefit of Involved-Field Radiotherapy for Patients With Relapsed-Refractory Hodgkin's Lymphoma With Incomplete Response Before Autologous Stem Cell Transplantation

IntroductionWe investigated for a possible role for peritransplantation involved-field radiotherapy (IFRT) by comparing patients who received IFRT before after autologous stem cell transplantation (ASCT) and patients who received salvage chemotherapy (CT) alone.Patients and MethodsWe retrospectively evaluated 73 consecutive patients with Hodgkin lymphoma treated with ASCT between 2003 and 2014. Twenty-one patients (28.8%) received peritransplantation radiotherapy. A Cox regression analysis (multivariate analysis; MVA) was performed to evaluate the prognostic role of any risk factor. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of ASCT. Response to CT and ASCT were evaluated with positron emission tomography (PET) scan.ResultsMedian follow-up was 41 months (range, 1-136 months). Overall, no significant difference appeared between patients who received IFRT and patients treated with CT alone; however, patients who were treated with IFRT had worse prognostic factors. In the MVA, advanced stage at relapse and persistent disease before ASCT (evident on PET scan [PET+]) were related to worse PFS and OS. In patients with limited stage disease at relapse and PET+, peritransplantation radiotherapy showed higher 3-year OS rates (91.7% vs. 62.3%) and PFS rates (67.5% vs. 50%) compared with patients treated with CT alone, although this difference was not significant (P = .14 and P = .22, respectively).ConclusionIFRT used before or after ASCT might partially compensate for worse prognostic factors among the overall population; subgroup analysis showed a trend for survival benefit at 3 years in patients with limited stage disease at relapse and PET+ before ASCT.     

An unusual site of presentation for Hodgkin's disease in the middle ear

We are presenting a case history of a patient with advanced Hodgkin's disease, who had secondary involvement of his middle ear. To our knowledge this is the first case report of such clinical presentation where radiation therapy was of good help for bringing about symptomatic relief. Possible routes of spread are discussed and the literature is reviewed.     

中胸段食管癌累及野与淋巴结选择性照射对比研究

目的：通过对中胸段食管癌累及野与淋巴结选择性照射的临床研究,为中胸段食管癌放疗方式选择提供参考依据。方法：选择2003—03—28—2007—04-02青岛大学医学院附属烟台毓璜顶医院接受同期化放疗的食管癌患者73例,采用抽签法随机分为累及野照射组（involved field irradiation,IFI）和局部淋巴结选择性照射组（elective nodal irradiation,END。随访观察两组患者的治疗毒副作用、失败情况、局部控制率和生存率。结果：IFI组〉Ⅲ级急性毒副作用发生率为14．3％（5／35）,明显低于ENI组的42．1％（16／38）,x2=10．531,P：0．001。IFI和ENI组的局部区域失败率分别为47．8％（11／23）和57．9％（11／19）,远处转移率分别为21．7％（5／23）和15．8％（3／19）,为失败的主要形式;野内复发率分别为43．5％（10／23）和43．4％（9／19）,为局部区域失败的主要方式。野外复发少见,分别为4．3％（1／23）和10．5％（2／19）。IFI组患者1、2和3年总生存率分别为71．8％、44．7％和25．7％,ENI组分别为66．1％、60．0％和45．4％,两组差异无统计学意义,r=0．586,P=0．444;IFI组1、2和3年局部控制率分别为93．0％、71．6％和71．5％,ENI组分别为87．0％、80．0％和80．0％,两组差异无统计学意义,r=0．281,P=0．596。T分期是重要的预后因素,x^2=0．521,P=0．045。结论：与淋巴结选择性照射相比,中胸段食管癌累及野照射可减少治疗毒副作用,而不降低肿瘤局部控制率及患者生存率。     

Second primary malignant neoplasms in patients treated for Hodgkin's disease at St Bartholomew's Hospital

The incidence of second malignant neoplasms (SMN's) was investigated in a group of 529 patients with Hodgkin's Disease (HD) treated at St Bartholomew's Hospital (SBH). SMN's were seen in 27 of these patients giving an incidence rate three and a half times that expected in an age and sex matched normal population (p = much less than 0.001). The incidence rate was higher in those receiving multiple chemotherapy and radiotherapy for relapsed HD compared with those receiving primary radiotherapy, chemotherapy or chemotherapy with adjuvant radiotherapy (p = 0.02). However, the increased incidence rate in those patients treated with chemotherapy on relapse, may reflect in part a delayed effect of their primary therapy, since the incidence rate in the primary treatment group only becomes significantly raised after six years. When allowance was made for this delay the difference between the two groups was no longer significant. The incidence rates for Non-Hodgkin's Lymphoma (NHL) and myelogenous leukaemia were 32 and 57 times those expected, compared with only two and a half times the expected rate for non-haematological SMN's (p = much less than 0.001). The four acute myeloid leukaemias (AML) all occurred within five years of treatment compared to wide-ranging intervals between treatment and occurrence of SMN in the other groups. The increased incidence of NHL may be an alternative expression of lymphoid abnormality rather than a treatment-related occurrence. Multiple SMN's were diagnosed in three patients. This represented a highly significant (p = much less than 0.001) increase over the expected incidence of multiple neoplasia in the general population. Several factors may contribute to the development of SMN's in HD, including an inherent disposition of HD itself. The time-dependent incidence pattern of SMN's with a delay followed by an increased incidence rate, suggests that treatment plays a key role. It is not yet clear whether more intensive, or multiple treatments add to the risk accrued for the initial treatment.     

Breast cancer following treatment for Hodgkin's disease: The need for screening in a young population

Several recent publications have highlighted the issue of an increased risk of breast cancer in women treated with radiotherapy, chemotherapy, or combined modality therapy for Hodgkin's disease. The risk is greatest in women 30 years or younger at the time of treatment. In the Australasian Radiation Oncology Lymphoma Group database, 60% of women fell into this age category. This article reviews the available data pertaining to induction of breast cancer by radiotherapy for Hodgkin's disease. Breast examination should now be an integral part of the long term follow up for these women. There is also a case for the use of screening mammography. Any breast mass developing subsequent to treatment for Hodgkin's disease should be regarded with a high index of clinical suspicion and, accordingly, biopsies should be performed in the majority of cases, even when mammography is negative.     

Evaluation of Acute and Early Cardiotoxicity in Survivors of Hodgkin's Disease Treated with ABVD or BEACOPP Regimens

Abstract

The study was conducted to compare the presence of cardiotoxicity after the treatment of Hodgkin's disease with the standard ABVD or BEACOPP protocol. We examined 29 patients treated by means of the ABVD regimen and 34 treated with the BEACOPP regimen. Using rest echocardiography we assessed the left ventricular function before and after the therapy. One year after the completion of therapy, a control examination was performed with a battery of tests; the rest and dynamic stress echocardiography and cardiopulmonary tests were carried out to assess cardiopulmonary performance. A similar significant deterioration of ejection fraction and diastolic function was apparent after the treatment in both sub-groups with a further progression at the one-year control. Only one patient from the BEACOPP sub-group showed a pathological drop of EF <50%. The most affected parameters of left ventricular function (LV) were Doppler indices. We found a significant relationship of the parameters of LV function compared with age, the cumulative dose of doxorubicin and the cumulative dose of radiotherapy. Multivariate analysis demonstrated that diastolic dysfunction correlated with advanced age and the cumulative dose of doxorubicin, and decreased cardiopulmonary performance with advanced age, radiotherapy, and female gender. Both parameters were significantly influenced by the presence of hypertension. The used regimens demonstrated similar subclinical cardiotoxicity, thus the most aggressive regimen, BEACOPP, is not accompanied by a higher rate of cardiac impairment. The clinical value of such subclinical cardiotoxicity will be estimated in a further prospective follow-up.     

The potential benefits of therapeutic splenectomy for patients with Hodgkin's disease and non-Hodgkin's lymphomas

Thirty-four patients with Hodgkin's disease and non-Hodgkin's lymphoma underwent therapeutic splenectomies to improve hematologic tolerance for chemotherapy. The mean age was 40 years; there were 16 males and 18 females. Fourteen had Hodgkin's disease, 19 had non-Hodgkin's lymphoma, and 1 had malignant histiocytosis. Nineteen had palpable splenomegaly, 19 had marrow involvement and 20 had splenic involvement by lymphoma. The following data were analyzed before and after splenectomy: mean white blood cell count (WBC) and platelet count on planned first day of cycle, delay ratio of chemotherapy delivery and percent maximal dose rate. Thirteen patients had non-Hodgkin's lymphoma, splenomegaly and positive bone marrow and showed significant benefit in all of the aforementioned parameters. Of the patients with prior irradiation, only those who completed their radiation greater than six months prior to splenectomy showed benefit. Ten patients had Hodgkin's disease, negative bone marrow and no splenomegaly. This group showed significant improvement in mean platelet count but more limited benefit in delay ratio and percent maximal dose rate. Thus, selected patients with lymphoma who are experiencing delays in chemotherapy because of poor count tolerance may benefit from splenectomy.