Hodgkin's disease limited to intrathoracic sites

The records of 1470 patients treated for Hodgkin's disease between 1960 and 1980 were reviewed, and sites of initial involvement were scored. Forty-four patients had disease limited to the chest after clinical and/or pathologic staging. Eighteen asymptomatic patients underwent a staging laparotomy and no occult subdiaphragmatic disease was identified. All 44 patients were treated with irradiation (XRT) to involved (IF), mantle (M), subtotal lymphoid (STLI), or total lymphoid (TLI) fields. Eighteen patients were also treated with chemotherapy, consisting of nitrogen mustard, vincristine, and procarbazine, with or without prednisone (MOP(P)), or procarbazine, melphalan, and vinblastine (PAVe). With a median follow-up of 7.5 years the survival at five and ten years was 93% and 89%, respectively, and the freedom from relapse (FFR) at five and ten years was 81% and 78%, respectively. Ten patients relapsed, all in supradiaphragmatic sites (including six relapses within lung parenchyma). Eight had initially received XRT alone, and two had received combined modality treatment. The risk of relapse in the 26 patients treated with XRT alone varied inversely with the volume irradiated: IF, 100% (3/3); M, 45% (3/7); STLI, 17% (2/12); TLI, 0% (0/4) relapsed. Seven of the eight relapsing patients treated with XRT alone were salvaged with subsequent XRT and/or chemotherapy whereas both of the combined modality patients who relapsed, died with progressive disease despite all salvage therapy.     

Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease.

PURPOSE: The management of early-stage Hodgkin's disease in the United States is controversial. To evaluate whether staging laparotomy could be safely avoided in early-stage Hodgkin's disease and whether chemotherapy should be a part of the treatment of nonlaparotomy staged patients, a phase III intergroup trial was performed. PATIENTS AND METHODS: Three hundred forty-eight patients with clinical stage IA to IIA supradiaphragmatic Hodgkin's disease were randomized without staging laparotomy to treatment with either subtotal lymphoid irradiation (STLI) or combined-modality therapy (CMT) consisting of three cycles of doxorubicin and vinblastine followed by STLI. RESULTS: The study was closed at the second, planned, interim analysis because of a markedly superior failure-free survival (FFS) rate for patients on the CMT arm (94%) compared with the STLI arm (81%). With a median follow-up of 3.3 years, 10 patients have experienced relapse or died on the chemoradiotherapy arm, compared with 34 on the radiotherapy arm (P <.001). Few deaths have occurred on either arm (three deaths on CMT and seven deaths on STLI). Treatment was well tolerated, with only one death on each arm attributed to treatment. CONCLUSION: These results demonstrate that it is possible to obtain a high FFS rate in a large group of stage IA to IIA patients without performing staging laparotomy and that three cycles of chemotherapy plus STLI provide a superior FFS compared with STLI alone. Extended follow-up is necessary to assess freedom from second relapse, overall survival, late toxicities, patterns of treatment failure, and quality of life.     

Reduction of fatal complications from combined modality therapy in Hodgkin's disease

A total of 464 pathologically staged IA through IIIB Hodgkin's disease patients were evaluated for the risk of developing acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, or a fatal infection after treatment with radiation therapy (RT) alone, initial combined radiation therapy and chemotherapy (CMT), or RT with MOPP administered at relapse. Patients received a standard six cycles of MOPP, and additional maintenance chemotherapy was not administered. Patients receiving total nodal irradiation (TNI) and MOPP chemotherapy have an 11.9% actuarial risk of developing a fatal complication at ten years, as compared to a 0.8% risk for lesser field irradiation and MOPP (P = .005). The risk with RT alone is 0.6%. Patients 40 years of age or older have a greater risk for complications. These data report a low risk for fatal complication with CMT when less than TNI is administered and when maintenance chemotherapy is not used.     

Occurrence of acute nonlymphocytic leukemia in a prospective randomized study of treatment for Hodgkin's disease

In a prospective randomized study of treatment with radiation therapy (RT) or RT followed by chemotherapy (CT) for patients with Hodgkin's disease stages I-III, four patients developed acute nonlymphocytic leukemia (ANLL) during post-treatment follow-up. There was a significant relationship between the intensity of the treatment and the appearance of this complication: no cases of ANLL were observed among the 128 patients treated with involved field (IF) RT, IF RT followed by CT, total nodal RT alone (TNR), or total lymphoid irradiation alone (TLI) after a follow-up from 21 to 126+ months (median follow-up 76 months). In contrast, four of 36 patients treated with extensive RT followed by CT developed ANLL at 17, 63, 72, and 91 months. Three of these patients had received TLI + CT, the fourth one TNR + CT.     

The role of radiation therapy in the management of stage III follicular lymphomas

Between 1961 and 1982, 66 patients with stage III follicular small cleaved (FSC) and follicular mixed small cleaved and large cell (FM) lymphoma were treated at Stanford University. Treatment consisted of total-lymphoid irradiation (TLI) to a total dose of about 4,000 rad in 61 patients or whole-body irradiation (WBI) followed by boost irradiation to sites of involvement in five patients. In addition, 13 patients treated with TLI received adjuvant chemotherapy, consisting of six cycles of cyclophosphamide, vincristine, and prednisone (CVP). Median follow-up was 9.6 years. Kaplan-Meier actuarial survival at five, ten, and 15 years was 78%, 50%, and 37%, respectively. Freedom from relapse at five and ten years was 60% and 40% with no relapses after ten years. In a prospective randomized study of 16 patients who all underwent staging laparotomy comparing TLI with or without adjuvant chemotherapy with CVP, there was no significant difference in either survival or freedom from relapse between the two groups. Patients with limited stage III disease (without B symptoms, less than five sites of involvement, and maximum size of disease less than 10 cm) had an excellent prognosis with a 15-year survival and freedom from relapse of 100% and 88%, respectively. Radiation therapy may be a potentially curative modality in patients with stage III follicular lymphomas.     

The Stanford experience with combined procarbazine, Alkeran and vinblastine (PAVe) and radiotherapy for locally extensive and advanced stage Hodgkin's disease.

This report describes the efficacy and toxicity of PAVe (procarbazine, Alkeran, vinblastine) and irradiation (RT) in the management of 159 patients with locally extensive or advanced stage Hodgkin's disease (HD) at Stanford University. Patients received six courses of chemotherapy alternating with RT. The extent of RT and the schedule of treatment varied according to the stage of disease. About 2/3 of patients received PAVe/RT in the setting of prospective, randomized clinical trials. The rate of complete response was 93%. With a median follow-up of seven years (range 2-17), the 15 year actuarial freedom from progression (FFP) is 78% and overall survival is 75%. Ten-year FFP by stage is: 80% for locally extensive stage II, 90% for stage IIIA and 70% for stage IIIB. Excellent and equal results were attained with PAVe/RT vs. MOP(P) (mustard, Oncovin, procarbazine with or without prednisone)/RT in the randomized combined modality studies. Progression or recurrence was documented in 30 patients and was more common in irradiated sites. PAVe was well tolerated acutely. There were no treatment related fatalities. Twenty-three (14%) patients were admitted to the hospital for neutropenic fever. Five second malignancies have occurred after PAVe/RT only: one myelodysplastic syndrome, one acute myelogenous leukemia, one non-Hodgkin's lymphoma and two solid tumors including a case of non-small cell lung cancer and an in situ carcinoma of the cervix. Three patients died from myocardial infarction several years after the completion of treatment. These mature data show that PAVe/RT is effective and well-tolerated therapy for locally extensive stage II and IIIA/B HD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Second neoplasms in patients with Hodgkin's disease following combined modality therapy--the Yale experience

From 1969 to 1982, 183 patients with previously untreated stages IIIB and IV Hodgkin's disease and relapsing Hodgkin's disease after radiation therapy were treated with combination chemotherapy plus low-dose irradiation (CRT). One hundred fifty patients who achieved a complete response (CR) were analyzed for risk of developing a second neoplasm. Median follow-up has been 8.3 years. Actuarial survival of all patients is 74% at 10 years with a relapse-free survival of 68%. An additional 24 patients with stage IIIA disease were also treated with CRT. There were 22 CRs at risk who were analyzed. Median follow-up has been 3+ years with an actuarial survival of 90% at five years and a relapse-free survival of 83%. Second neoplasms have developed in 14 of 172 patients at risk: acute nonlymphocytic leukemia (ANLL; five patients); aggressive histology non-Hodgkin's lymphoma (NHL; three patients); and a variety of solid neoplasms (six patients). Time to second neoplasm diagnosis after initial treatment ranged from 12 to 141 months. Five patients were older than 40 years. At the time of diagnosis of the second malignancy, 11 patients were free of Hodgkin's disease (for 36 to 141 months) and three were receiving therapy for recurrent Hodgkin's disease. The 10-year actuarial risk (%) of developing ANLL was 5.9 +/- 2.8; for NHL, the risk was 3.5 +/- 2.4, and for solid neoplasms, 5.8 +/- 3.0. Our results suggest that combination chemotherapy plus low-dose irradiation does not appear to significantly increase the risk of developing second neoplasms above that already reported for combination chemotherapy when administered as either initial or salvage treatment of Hodgkin's disease.     

Results of a prospective trial of mantle irradiation alone for selected patients with early-stage Hodgkin's disease.

PURPOSE: To determine the efficacy of mantle radiation therapy alone in selected patients with early-stage Hodgkin's disease. PATIENTS AND METHODS: Between October 1988 and June 2000, 87 selected patients with pathologic stage (PS) IA to IIA or clinical stage (CS) IA Hodgkin's disease were entered onto a single-arm prospective trial of treatment with mantle irradiation alone. Eighty-three of 87 patients had > or = 1 year of follow-up after completion of mantle irradiation and were included for analysis in this study. Thirty-seven patients had PS IA, 40 had PS IIA, and six had CS IA disease. Histologic distribution was as follows: nodular sclerosis (n = 64), lymphocyte predominant (n = 15), mixed cellularity (n = 3), and unclassified (n = 1). Median follow-up time was 61 months. RESULTS: The 5-year actuarial rates of freedom from treatment failure (FFTF) and overall survival were 86% and 100%, respectively. Eleven of 83 patients relapsed at a median time of 27 months. Nine of the 11 relapses contained at least a component below the diaphragm. All 11 patients who developed recurrent disease were alive without evidence of Hodgkin's disease at the time of last follow-up. The 5-year FFTF in the 43 stage I patients was 92% compared with 78% in the 40 stage II patients (P =.04). Significant differences in FFTF were not seen by histology (P =.26) or by European Organization for Research and Treatment of Cancer H-5F eligibility (P =.25). CONCLUSION: Mantle irradiation alone in selected patients with early-stage Hodgkin's disease is associated with disease control rates comparable to those seen with extended field irradiation. The FFTF is especially favorable among stage I patients.     

Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial.

PURPOSE: To provide more mature data on the efficacy and complications of a brief, dose-intense chemotherapy regimen plus radiation therapy (RT) to bulky disease sites for locally extensive and advanced-stage Hodgkin's disease. PATIENTS AND METHODS: One hundred forty-two patients with stage III or IV or locally extensive mediastinal stage I or II Hodgkin's disease received Stanford V chemotherapy for 12 weeks followed by 36-Gy RT to initial sites of bulky (> or =5 cm) or macroscopic splenic disease. Freedom from progression (FFP), overall survival (OS), and freedom from second relapse (FF2R) were determined using life-table estimates. Outcomes were analyzed according to the international prognostic score. Late effects of treatment were recorded in follow-up. RESULTS: With a median follow-up of 5.4 years, the 5-year FFP was 89% and the OS was 96%. No patient progressed during treatment, and there were no treatment-related deaths. FFP was significantly superior among patients with a prognostic score of 0 to 2 compared with those with a score of 3 and higher (94% v 75%, P <.0001). No secondary leukemia was observed. To date, there have been 42 pregnancies after treatment. Among 16 patients who relapsed, the FF2R was 69% at 5 years. CONCLUSION: These data confirm our preliminary report that Stanford V chemotherapy with RT to bulky disease sites is highly effective in locally extensive and advanced Hodgkin's disease. It is most important to compare this approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the ongoing intergroup trial (E2496) to determine whether Stanford V with or without RT represents a therapeutic advance.     

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) 10 IU/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 (6 IU/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 (OS) at five years are 75% (95% CI, 60.1%-92.2%) and 85% (95% CI, 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.     

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.     

Treatment of pathologically staged IIIA Hodgkin's disease

We have reviewed the records of 37 patients with pathologically staged IIIA Hodgkin's disease, treated from 1970 to 1982. Twenty patients were staged IIIA1 and 17 staged IIIA2. Treatment consisted of total nodal irradiation in 33 patients (eight of whom received adjuvant MOPP), and mantle plus para-aortic irradiation in four patients (all of whom received adjuvant MOPP). Five-year relapse-free survival (RFS) in patients without splenic involvement was 77% versus 49% for those with splenic involvement (p = 0.43). Five-year RFS in patients treated with irradiation and chemotherapy (RT/CT) was 76% vs. 47% for patients treated with irradiation alone (p = 0.12). RFS was not influenced by sex, mediastinal involvement by tumor, or anatomic substage. Overall survival (corrected for deaths due to intercurrent disease) for the entire group of patients was 92% at 5 years and 87% at 10 years. Sex, mediastinal or splenic involvement by tumor, therapy (RT vs. RT/CT), or anatomic substage did not significantly influence survival. We currently recommend RT/CT only for those patients with extensive splenic involvement and/or Stage IIIA2 disease. We feel that the poor prognosis of these patients justifies the use of RT/CT and its risk of second malignancies.     

High-dose cytotoxic therapy and bone marrow transplantation for relapsed Hodgkin's disease

Patients with Hodgkin's disease who have failed two or more chemotherapy regimens or who have relapsed after an initial chemotherapy-induced remission of less than 12 months are seldom cured with conventional salvage therapies. We studied the effect of high-dose cytoreductive therapy followed by bone marrow transplantation in 50 such patients with relapsed Hodgkin's disease. Twenty-one patients with histocompatibility locus antigen (HLA)-matched donors had allogeneic marrow transplants, one patient received marrow from an identical twin, and 28 patients without a matched donor received autologous grafts purged with 4-hydroperoxycyclophosphamide. Busulfan plus cyclophosphamide was the preparative regimen for the 25 patients who had received extensive prior irradiation, and the other 25 patients received cyclophosphamide plus total body irradiation. The overall actuarial probability of event-free survival at 3 years was 30%, with a median follow-up of 26 months. The event-free survival following transplantation was influenced by the number of chemotherapy failures and the patient's response to conventional salvage therapy prior to transplant. The 16 patients who were transplanted at first relapse, while still responsive to standard therapy, had a 64% actuarial probability of event-free survival at 3 years. Age, presence of extranodal disease, preparative regimen, and type of graft (autologous v allogeneic) were not significant prognostic factors. The majority of transplant-related deaths were from interstitial pneumonitis; inadequate pulmonary function, multiple prior chemotherapy regimens, and prior chest irradiation all appeared to increase the transplant-related mortality. These results suggest a role for marrow transplantation in a subset of patients with relapsed Hodgkin's disease who are unlikely to be otherwise cured but are still responsive to conventional-dose cytoreductive therapy.     

A meta-analysis of stages I and II Hodgkin's disease

To compare radiotherapy alone to chemotherapy plus radiotherapy in the treatment of early stage Hodgkin's disease, the English language medical literature was searched for reports on randomized clinical trials in Stages I and II Hodgkin's disease from 1975 through 1986. Twenty-three reports with 2999 patients were entered into matched study analysis. Data on extended-field radiotherapy (EF), involved-field (IF), chemotherapy alone, combination chemotherapy and radiotherapy (CM), disease stage, laparotomy staging, and complications were gathered. A proportional hazard rate was used to estimate and compare relapse-free (RFS) and overall survival rates (S). Iteratively reweighted least square analysis was used to estimate survival curves. Twelve-year RFS for CM (889 patients) was significantly superior to EF (1350 patients) (P less than 0.01). Twenty-year RFS in EF was better than IF (760 patients) (P less than 0.01). Twelve-year S for CM was not significantly different than for EF but was better than for IF (P less than 0.05).     

Carcinoma of the nasopharynx. An analysis of 91 cases and a comparison of differing treatment approaches

Ninety-one patients with malignant epithelial tumors of the nasopharynx seen in our department from 1970 to 1982 were evaluated. The 5- and 10-year actuarial survival rates were 62.0% and 42.0%, respectively. Patients seen from 1970 to 1979 were treated by radiotherapy to the primary site and upper neck, the lower neck being irradiated only in instances of massive disease. Those treated from 1980 to 1982 received elective irradiation of the whole neck, as well as adjuvant chemotherapy (consisting of cyclophosphamide, methotrexate, and either 5-fluorouracil or bleomycin) for 6 to 12 months after completion of radiotherapy. Comparison of 3-year actuarial survival (61.4% versus 83.3%) and disease-free survival (49.7 versus 77.0%) rates show significantly improved results (P less than 0.05) for those receiving combined therapy. In addition, significantly fewer (P less than 0.05) distant metastases appeared in the combined therapy group at 18 months. A retrospective analysis comparing those patients who received full-neck irradiation and adjuvant chemotherapy with those who received full-neck irradiation alone showed a significantly improved survival (P less than 0.02) and disease-free survival (P less than 0.05) for those patients with undifferentiated carcinomas, including lymphoepitheliomas, who received adjuvant chemotherapy.     

Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group.

PURPOSE: We report results of a randomized trial comparing ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy alone with treatment that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma. PATIENTS AND METHODS: Patients with nonbulky clinical stage I to IIA Hodgkin's lymphoma were stratified into favorable and unfavorable risk cohorts. Patients allocated to radiation-containing therapy received subtotal nodal radiation if favorable risk or combined-modality therapy if unfavorable risk. Patients allocated to ABVD received four to six treatment cycles. RESULTS: We evaluated 399 patients. Median follow-up is 4.2 years. In comparison with ABVD alone, 5-year freedom from disease progression is superior in patients allocated to radiation therapy (P = .006; 93% v 87%); no differences in event-free survival (P = .06; 88% v 86%) or overall survival (P = .4; 94% v 96%) were detected. In a subset analyses comparing patients stratified into the unfavorable cohort, freedom from disease progression was superior in patients allocated to combined-modality treatment (P = .004; 95% v 88%); no difference in overall survival was detected (P = .3; 92% v 95%). Of 15 deaths observed, nine were attributed to causes other than Hodgkin's lymphoma or acute treatment-related toxicity. CONCLUSION: In patients with limited-stage Hodgkin's lymphoma, no difference in overall survival was detected between patients randomly assigned to receive treatment that includes radiation therapy or ABVD alone. Although 5-year freedom from disease progression was superior in patients receiving radiation therapy, this advantage is offset by deaths due to causes other than progressive Hodgkin's lymphoma or acute treatment-related toxicity.     

Two cycles of MOPP and radiotherapy for stage III1A and stage III1B Hodgkin's disease

One hundred two adult patients with stage III1A (76 patients) and stage III1B (26 patients) Hodgkin's disease were treated with two cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and radiotherapy (XRT) between 1970 and 1984. Sixty-four of the patients were treated between 1970 and 1978 with two cycles of MOPP and XRT to the mantle, upper abdomen, and pelvis. The remaining 38 patients were treated from 1978 to 1984 with a modification of the protocol in which pelvic XRT was omitted and low-dose whole-lung XRT was administered to patients with unfavorable mediastinal disease. The 10-year actuarial freedom-from-progression (FFP) and determinate survival rates at a mean follow-up of 93 months were 84% and 86% for stage III1 disease, 86% and 84% for stage III1A disease, and 78% and 91% for stage III1B disease. Three patients died of treatment-related toxicities without evidence of Hodgkin's disease, two died of complications of myelosuppression and one of acute nonlymphocytic leukemia (ANLL). Neither FFP nor determinate survival rates were significantly influenced by B symptoms, unfavorable mediastinal disease, histologic subtype, extent of abdominal disease, the omission of pelvic XRT, the use of whole-lung XRT, or the number of splenic nodules. Patients 40 years of age or older had a 73% determinate survival rate at 10 years compared with 88% for patients younger than 40 years (P = .01). This survival difference was due to treatment-related toxicity in the older group. This study indicates that two cycles of MOPP and XRT to the mantle and upper abdomen is as effective as more intensive treatment for all patients with stage III1 Hodgkin's disease. This treatment program can preserve fertility and has had only a 1% actuarial incidence of ANLL at 15 years.     

Stage III Hodgkin's disease: improved survival with combined modality therapy as compared with radiation therapy alone

This is a retrospective analysis of 120 patients with pathologically stage IIIA and IIIB Hodgkin's disease treated from April 1969 to December 1982. The median follow-up was 108 months. Treatment consisted of radiation therapy (RT) alone in 54 patients and combined radiation therapy and MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy (CMT) in 66 patients. Stage III patients treated with CMT have an improved actuarial 12-year survival as compared with patients treated with RT alone with MOPP reserved for relapse (80% v 64%; P = .026). The 12-year actuarial freedom from first relapse by treatment for stage III patients is 83% and 40%, respectively (P less than .0001). Improved survivals following combined modality therapy are seen for the following subgroups of stage III patients: stage III2, 66% (CMT) v 44% (total nodal irradiation; TNI), P = .04; stage III1, 97% (CMT) v 73% (TNI), P = .05; stage III mixed cellularity or lymphocyte depletion histology, 94% (CMT) v 65% (TNI), P = .007; and stage III extensive splenic involvement, 77% (CMT) v 58% (TNI), P = .02. These survival differences are not seen in patients with nodular sclerosis or lymphocyte predominance histology or in patients with minimal splenic involvement. These data indicate that the initial use of CMT in stage III Hodgkin's disease results in an improved survival as compared with initial treatment with RT with MOPP reserved for relapse. Patients with limited Stage IIIA disease may still be candidates for radiation therapy alone.     

The impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity in early-stage Hodgkin's disease

A retrospective analysis of patients with supradiaphragmatic Stage I-II Hodgkin's disease was performed to assess the impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity. One hundred twenty patients were treated with radiotherapy (RT) alone; 38 received total nodal (including pelvic) irradiation (TNI), 63 received modified total nodal (excluding pelvic) irradiation (MTNI), and 19 received involved-field or mantle irradiation only (less than MTNI). Thirty-three patients received combined-modality therapy. In laparotomy-staged (PS) patients treated with RT alone, the overall treatment failure rate was 13% after TNI, 24% after MTNI, and 43% after less than MTNI. The pelvic failure rate in PS patients was 0% after TNI, 9% after MTNI, and 29% after less than MTNI. Cause-specific deaths in patients treated with RT alone occurred in 10% following less than MTNI, 13% following MTNI, and 10% following TNI. Cause-specific deaths due to pelvic failure in patients treated with RT alone occurred in 5% following IF and 6% following MTNI, and also occurred in 7% of patients receiving combined-modality therapy. The potential disadvantages of elective pelvic irradiation in early-stage Hodgkin's disease include compromise of future tolerance of chemotherapy in the event of treatment failure, and infertility. Gonadal function was assessed in 67 patients less than 35 years old at the time of treatment. Compromise of gonadal function was correlated with the lack of special testicular shielding during pelvic irradiation and chemotherapy in the male, and with no oophoropexy before pelvic irradiation in the female. Twelve of 26 patients with recurrence after either less than MTNI or MTNI, with or without chemotherapy, were alive and without evidence of disease at greater than 2 years after completing salvage therapy, compared with 7 of 11 patients with recurrence after TNI.     

Treatment of pediatric Hodgkin's disease with chemotherapy alone or combined modality therapy

Optimal treatment for Hodgkin's disease during childhood is unknown. We report the treatment outcome of patients with Hodgkin's disease <13 years of age seen at the American University of Beirut Medical Center (AUBMC) between 1980 and 1996. A retrospective review of the medical records of 24 children treated for HD at AUBMC was performed. Treatment consisted of chemotherapy alone (n = 15) or chemotherapy plus involved field radiotherapy (n = 9). Chemotherapy consisted of COPP, ABVD, or alternating cycles of each for a total of 6 to 12 cycles, depending on clinical and radiological response; three patients received MOPP. Five patients in the chemotherapy group had clinical stage (CS) I and II and 10 had CS III disease. In the combined modality group, eight patients had CS I and II and one had CS IV disease. At a median follow-up of 5 years, the event-free survival (EFS) for the combined modality group was 100% and the overall survival (OS) 100%. For the chemotherapy alone group, the EFS was 56% and the OS was 79%. Four patients (27%) in the chemotherapy alone group who had Stage IIIB disease relapsed. Mean time to relapse was 4.3 years. In our experience, six cycles of COPP or (COPP plus ABVD) alone were suboptimal for the treatment of Stage IIIB Hodgkin's disease patients, especially those with involvement of lower abdominal nodes (III2B), extensive pulmonary disease, or mixed cellularity histology. Radiation therapy or additional chemotherapy courses are required for these patients.