Radiation therapy treatment of stage I and II extranodal non-Hodgkin's lymphoma of the head and neck

We have reviewed the records of 76 patients with Stage I or II extranodal non-Hodgkin's lymphoma who were referred to the Division of Radiation Oncology, Mallinckrodt Institute of Radiology, during the years 1964 through 1974. The histologic slides were reviewed in the 67 cases in which they were available. Forty-three percent of Ann Arbor Stage I and II patients relapsed after primary radiation treatment.Seventy-three percent of these failed in sites distant from the irradiated volume. Failures in the treated volume were infrequent (7%) except in those patients presenting with primary lesions of the brain (4/5). Those patients presenting with lesions of Waldeyer's ring experienced a decrease in survival with increasing tumor size. Because of the high rate of failure in distant sites with tumors in the lingual and palatine tonsils, we are recommending the study of adjuvant chemotherapy in these cases, after primary radiation treatment.     

Results of radiation therapy of stage I non-Hodgkin's lymphoma of Waldeyer's ring

The treatment records of 107 patients with stage I diffuse non-Hodgkin's lymphoma of the Waldeyer's ring, who were irradiated at 7 institutions from 1972 through 1985, were analyzed. The local control rate, the 5 year actuarial survival rate and the 5 year relapse-free survival rate were 96.4%, 76.2% and 76.6%, respectively. Any high risk group could not be found in the pathological subtype, the initial site of the tumor and the tumor size. There were 17 relapse cases within the first 2 years after radiotherapy. Most relapse occurred in the distant site from the irradiated field. With these results, the treatment policy of Waldeyer's ring lymphoma of stage I was discussed.     

Chemotherapy followed by consolidation radiation therapy for the treatment of clinical stage II aggressive histologic type non-Hodgkin's lymphoma

Sixty-three eligible patients with Ann Arbor clinical Stage II or IIE aggressive histologic type non-Hodgkin's lymphomas received combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [COPA]) as the primary treatment technique. Moderate-dose radiation therapy (2500 to 3000 cGy in 2 to 3 weeks) was given to anatomic areas involved initially by lymphoma in patients demonstrated to be in complete remission after chemotherapy. Fifty-seven percent of the patients were free of lymphoma clinically after induction chemotherapy. The minimum patient follow-up from the start of chemotherapy is 3.7 years, and the median follow-up for patients still alive is 4.7 years. The progression-free survival is projected to be 62% at 4 years, and 86% of the patients achieving a complete response are projected to be in continuous remission at 4 years from the completion of all therapy. There were no treatment-related fatalities. This treatment sequence has produced durable tumor control in the majority of patients with acceptable toxicity. The need for consolidation radiation therapy is being studied currently in a controlled clinical trial.     

Role of radiation therapy in localized non-Hodgkin's lymphoma

Relapse occurs in 50% of patients receiving radiation for clinical stage (C.S.) I and II nodal and extranodal non-Hodgkin's lymphoma (N.H.L.). Prior to the introduction of intensive chemotherapy those failing primary control with irradiation and most of those who relapsed died of their disease with a resultant overall mortality of 50%. An analysis of Princess Margaret Hospital results with radiation for C.S. I and II N.H.L. between January 1967 and December 1978 revealed that tumour bulk, age, stage and histology were of independent prognostic significance. It was possible to group patients using combinations of these attributes so that each group encompassed only patients with similar outcomes. Such prognostic groups were identified separately within the low grade and the intermediate plus high grade categories of the Working Formulation. Patients with a high probability of cure with radiation were so defined. Also those patients in whom chemotherapy would be optimal initial therapy were also defined. Such patients were in the intermediate plus high grade histology groups. Thirty percent of all patients with low grade histology lymphoma had an actuarial survival of 83%, and relapse-free rate of 63% at 10 years. By implication, approximately 20% of all patients with these histologies seen at the Princess Margaret Hospital for the same time period achieved prolonged relapse-free survival by localized therapy. This is at variance with the implications of staging from studies where laparotomy and multiple bone marrow biopsies have been used. Such aggressive staging procedures suggest truly localised disease in only 5-6% of patients with low grade lymphoma. A significant relationship between radiation dose and disease control was demonstrated only for patients with intermediate and high grade lymphoma of medium or large bulk. A minimum tumour dose of 30 Gy was required for optimal local control with radiation.     

Modified CHOP therapy in patients with non-Hodgkin's lymphoma

From July 1983 to December 1989, 31 previously untreated patients with non-Hodgkin's lymphoma were treated with modified CHOP regimen (cyclophosphamide 300 mg/m2 on day 1, aclacinomycin 40 mg/m2 on day 1, vincristine 0.7 mg/m2 on day 1 and prednisolone 40 mg/m2 on days 1-5). The therapy was repeated at 2-week intervals. The complete response rate was 66.7% for clinical stage (CS) II according to the Ann Arbor criteria, 60.0% for CS III and 33.3% for CS IV, respectively. The 5-year survival rate was 100% for CS II, 36.6% for CS III and 34.6% for CS IV, respectively. Clinical effects of modified CHOP regimen were almost the same as those of other therapies including adriamycin from the standpoint of 5-year survival rate. On the other hand, the myelosuppression accompanying modified CHOP therapy was not severe. Only one patient had a white blood count below 1,000/microliters during 6 courses of the therapy. It is thought that this regimen is useful to enhance the quality of life of patients because of no severe complications such as myelosuppression.     

Salvage therapy for patients with non-Hodgkin's lymphoma

The non-Hodgkin's lymphomas represent a diverse group of lymphoproliferative disorders for which treatment must be specified according to the patient's status as well as the disease status. Although many advances have been made in the front-line treatment of non-Hodgkin's lymphomas, more than 50% of the patients will not be cured with their initial therapy. Because of these treatment failures with front-line therapy, many different salvage therapies have been tried in this patient population. In this article, we describe several conventional-dose, salvage chemotherapies and strategies for dose escalation and hematopoietic stem cell transplantation in an attempt to overcome chemotherapy resistance.     

Results of radiation therapy in extranodal non-Hodgkin's lymphoma of the head and neck--a study of the Japan Lymphoma Radiation Therapy Study Group

Extranodal non-Hodgkin's lymphoma (NHL) in the head and neck except Waldeyer's ring treated with radiation were analyzed. No definite difference was observed both in actuarial and relapse-free five-year survival rate between stage I and II. There was a high survival rate with orbital NHL in which most of the patients occupied with favorable histology. Prognosis of the disease was highly influenced by the histologic subtype; five-year survival was 91.4% in DWDL, 77.2% in the DM, 52.0% in DPDL and 51.7% in DH. Application of histologic classification with the Working Formulation was also recommended. There was a high incidence of extranodal relapses to bone and/or soft tissue from the lesions with nasal cavity, paranasal sinus and oral cavity.     

The role of radiation therapy in the management of non-Hodgkin's lymphoma

For patients with stage I-II malignant lymphoma with low-grade malignancy, five-year survival rates after radiation therapy are 75-100%. For patients with intermediate malignancy, five-year survival rates after radiation therapy alone are 70-100% for patients with pathological stage I-II and 45-75% for clinical stage I-II. Radiation dose to the tumor at least 40 Gy was required to produce consistent local control. Initial use of chemotherapy with radiation therapy is indicated to improve relapse-free survival rate for patients with clinical stage I-II, as well as pathological stage I-II.     

Results of radiotherapy in patients with stage I orbital non-Hodgkin's lymphoma

This paper describes the results of radiotherapy in early stage orbital non-Hodgkin's lymphoma. From 1970 to 1985, 33 orbital localizations in 30 patients were treated. The total dose applied ranged from 21 to 57 Gy (2 Gy per fraction), two-thirds of all patients received a dose of 40 Gy. The complete-response rate was 94% and the 10 years actuarial survival was 90%; no significant difference in survival was observed between patients with low grade or intermediate grade lymphoma. No local recurrence was detected during follow up and 20% of the patients developed generalized disease. Two optic nerve neuropathies and three retinopathies were observed in five patients, four of these occurred at a dose level of less than 43 Gy. Keratitis occurred in 58% of the patients treated, a sicca syndrome in 30% and cataract of different grades in 58% of the patients treated. Although local control was excellent, severe complications were observed in 13% of the patients who received a dose of less than 43 Gy.     

External beam radiation therapy for prostate cancer

Men with non-metastatic prostate cancer have many treatment options. For over 35 years, radiation therapy has been a mainstay of treatment for this disease. With improvements in technology and better use of pretreatment prognostic factors, such as prostate specific antigen level and Gleason score, biochemical and clinical results have steadily improved. This article reviews the current status of radiation therapy in the treatment of prostate cancer. Results of treatment utilizing three-dimensional conformal and conventional techniques are compared and contrasted. The appropriate use of adjuvant hormones and particle beam therapy in the management of this disease is also discussed. Finally, the toxicity and future directions of radiation therapy in the treatment of prostate cancer are addressed.     

A systematic overview of radiation therapy effects in non-Hodgkin's lymphoma

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for non-Hodgkin's lymphoma (NHL) is based on data from seven randomized trials. Moreover, data from 17 prospective studies, 22 retrospective studies and 27 other articles were used. In total, 73 scientific articles are included, involving 13,305 patients. The results were compared with those of a similar overview from 1996 including 14,137 patients. The conclusions reached can be summarized as follows: Indolent lymphomas. Data indicate that one-third to one-half of patients with indolent lymphoma in stage I are cured by radiotherapy (follow-up more than 15 years). Addition of chemotherapy to radiotherapy does not indicate any improvement in overall outcome. Optimal radiation dose is not defined and extended field is not superior to involved field. Aggressive localized lymphomas. Data indicate that half of the patients in stage I are cured by radiotherapy alone. Although randomized and non-randomized studies favour combined modality treatment with chemotherapy followed by radiotherapy instead of radiotherapy or chemotherapy alone in localized disease, no firm conclusions can be drawn. Conflicting data have been published on the value of radiotherapy towards bulky disease and no firm conclusions can be drawn. Optimal dose for radiation alone or after chemotherapy has not been established. Total body irradiation (TBI). The value of TBI for treatment of NHL has not been proven. There is no proof that fractionated TBI in conjunction with high-dose chemotherapy is superior to chemotherapy regimens alone. Primary CNS lymphomas. Data show that radiotherapy induces a response of short duration and is associated with major neurotoxicity, especially in elderly patients. High-dose methotrexate therapy seems to lead to longer survival than radiotherapy alone. No randomized trials have been performed. There is fairly good support for primary chemotherapy including high-dose methotrexate followed by radiotherapy in patients below 60 years. To minimize the risk of neurotoxicity of combined modality treatment it has been proposed to use chemotherapy alone and delay radiotherapy for relapse, especially in patients above 60 years, or use it in chemotherapy-resistant disease. Optimal chemotherapy regimen is not defined and the role of radiotherapy remains to be determined. Head and neck lymphomas. There is some support for combined modality treatment with chemotherapy and radiotherapy for aggressive lymphomas in Waldeyer's ring with limited disease. There are sparse data supporting radiotherapy alone in localized indolent lymphomas in salivary glands. Radioimmunotherapy (RIT). Radioimmunotherapy is a new treatment modality with systemic radiation for patients with advanced NHL, where conventional external beam radiotherapy plays only a minor role. Several phase I and II studies with RIT have documented promising results. A variety of monoclonal antibodies, radionuclides and study designs with both myeloablative and non-myeloablative approach have resulted in high response rates in patients with recurrent or refractory NHL. One randomized clinical trial is published, showing superior therapy results with radiolabelled antibody compared with the corresponding unlabelled antibody.     

Results of radiation therapy of extranodal non-Hodgkin's lymphoma of the head and neck--a study of the Japan Lymphoma Radiation Therapy Study Group

During the years 1972-81, 168 patients with extranodal Non-Hodgkin's lymphoma localized in the head and neck were treated with radiation. Five-year survival rates were 62% in stage I, 56% in stage II, and 91% in diffuse well-differentiated lymphocytic, 77% in diffuse mixed, 52% in diffuse poorly-differentiated lymphocytic and diffuse histiocytic each. Marginal relapse was rare after radiation therapy, but relapses were not infrequently noticed in distant extranodal sites. Bone and/or soft tissue relapses were frequently noticed in patients with lesions initially located in the nasal cavity, paranasal sinus and oral cavity.     

早期结外鼻型NK/T细胞淋巴瘤同期放化疗疗效分析

目的:探讨Ⅰ E～ⅡE期结外鼻型NK/T细胞淋巴瘤同期放化疗的疗效,并进一步分析其可行性.方法:回顾分析18例早期结外鼻型NK/T细胞淋巴瘤患者,以序贯化放疗50例为对照.18例同期放化疗患者中诱导化疗+同期放化疗+辅助化疗3例,诱导化疗十同期放化疗13例,同期放化疗十辅助化疗1例,单纯同期放化疗1例,全组放疗中位剂量54 Gy.结果:诱导化疗后的总缓解率为50.0％(8/16),治疗结束后为100.0％(18/18).同期放化疗组与对照组的5年总生存率分别为80.8％和54.3％(x2=3.66,P=0.05),5年无进展生存率(PFS)分别为75.8％和43.3％(x2=6.13,P=0.01),5年局部控制(LC)率分别为94.1％和56.7％(x2=6.32,P-0.01).同期放化疗过程中出现Ⅲ～Ⅳ度骨髓抑制率为27.8％(5/18),Ⅲ度口腔黏膜反应率为16.7％(3/18),Ⅲ度咽喉反应率为5.6％(1/18),其余不良反应均 为Ⅰ～Ⅱ度,Ⅲ～Ⅳ反应经对症处理后未影响下一步治疗.结论:同期放化疗是早期结外鼻型NK/T细胞淋巴瘤安全、有效的治疗方法,相对其他接受放疗患者有提高局部控制率和生存时间的趋势,其毒副反应可以耐受.     

Primary extranodal non-Hodgkin's lymphoma of the head and neck.

Among 387 cases of non-Hodgkin's lymphoma (NHL) treated in our units between January 1977 and December 1990, 52 (13.4%) had primary extranodal (PE) NHL of the head and neck. The median age was 55 years with a M:F ratio of 1.9:1. The most frequent primary site was the tonsil (28 cases), followed by oral cavity, parotid gland, orbit and other sites. The aggressive histological subtypes predominate. 55.2% of the patients were in stage I and 44.8% in stage II of disease. The CR rate was high (94.2%). The 5 years' overall survival rate was 65% and it was influenced mainly by stage (stage I 82.5% vs. 48.7% in stage II). Sex, age and histology did not significantly affect survival rate. Patients with primary Waldeyer's ring involvement (WR group) did not differ significantly from the other primary sites analyzed as a group (non-WR group) in respect to median age, sex distribution, histology and CR rates. They differed, however, in: (1) stage distribution with stage II disease more frequent in the WR group; (2) overall survival and disease-free survival both of which were significantly better in the non-WR group; and (3) the high incidence of GI tract involvement as initial manifestation of relapse in the WR group. It is concluded that the behaviour of the Waldeyer's ring PE-NHL is rather distinctive and should be considered separately from the other PE-NHL of the head and neck.     

Impact of highly active antiretroviral therapy in the treatment of HIV-infected patients with systemic non-Hodgkin's lymphoma

Twenty cases of systemic non-Hodgkin's lymphoma (NHL) in HIV-infected patients were reviewed over a 10-year-period, divided into Group A, including 13 NHL cases treated before the highly active antiretroviral therapy (HAART) era, and Group B, including 7 patients who received HAART. A Kaplan-Meier survival curve was performed and log-rank was applied to assess statistical differences between the groups. In group A, the median CD4 count was 36 cells/mm 3 . No complete remission was found. In group B, the median CD4 count was 137 cells/mm 3 . Four patients (57.0%) are still alive and in complete remission. Group A had a median survival of 5 months and group B 31 months (p=0.0032). Our results are in agreement with recent reports in that a higher CD4 count and better immune status achieved with HAART is predictive of a better outcome. We found that HAART in combination with chemotherapy improves overall survival of NHL patients without increasing adverse effects.     

Reduced-dose chop therapy for elderly patients with non-Hodgkin's lymphoma

While CHOP therapy is effective for malignant lymphoma, the optimum schedule for elderly patients remains controversial. The present study investigated the usefulness of reduced-dose CHOP therapy for elderly patients. Previously untreated patients aged 65 years or older with intermediate to high-grade non-Hodgkin's lymphoma were given up to 6 courses of reduced-dose CHOP therapy at 3-week intervals. Group A patients were given (5/6) of the standard dose and Group B received 7/12 of the standard dose. Filgrastim was administered when the white blood cell count fell below 2,000/microL. Fifty-seven patients were evaluable and the scheduled therapy was completed in 37. For patients aged from 65 to 79 years and for patients older than 80 years, the complete response rate was 79.5% and 46.2%, overall 3-year survival was 58.2% and 30.4%, and event-free 3-year survival was 49.3% and 44.4%, respectively. Major toxicities (> or = grade 3) included leukopenia in 42 patients and documented infection in 7 patients. Grade 3 cardiac plus renal failure, grade 3 peritonitis due to small bowel perforation, and grade 3 liver dysfunction occurred in 1 patient each. One patient died of toxicity (grade 4 hematological toxicity and pneumonia). In conclusion, it seems that in the elderly patients with non-Hodgkin's lymphoma, response to reduced-dose ((5/6) dose) CHOP therapy is comparable to that for standard CHOP in younger adults, mainly because of improved dose-intensity.     

The role of radiation therapy in the treatment of early stage large cell lymphoma

Nineteen patients with localized non-Hodgkin's lymphoma large cell type classified by the international formulation in group D (5) and group G (14) were treated with extended field radiation therapy. These patients have been followed for 168 months with range from 12 to 168 months from initiation of treatment. In G category of the formulation, the overall survival is 83 per cent at 5 and 10 years and recurrence-free survival is 75 per cent at 10 years. Sixteen of the patients were stage I and three were stage II. Two patients died without evidence of recurrence. Four patients recurred and two of these died of disease. Thirteen of the 19 patients are alive and recurrence free. Bulk of disease had no apparent influence on the response to irradiation. We believe that the early pathological stage large cell lymphoma of the G and D type international formulation are appropriate candidates for radical radiation therapy and benefit from this approach to treatment.     

AIDS-related non-Hodgkin's lymphoma: the outcome and efficacy of radiation therapy

The records of all 16 patients with AIDS-related lymphoma treated with radiation therapy at our institutions were reviewed. All patients were male with a median age of 32 years, and all but one had biopsy proven high-grade NHL. Eleven had lymphoma involving the central nervous system and five had lymphoma involving other sites. Seven of the 11 patients with CNS involvement had primary CNS lymphoma. All patients were treated with megavoltage X rays to doses ranging from 1050 cGy in 1 1/2 weeks to 5037 cGy in 6 weeks. Of those patients with CNS lymphoma, only one responded completely and four responded partially to irradiation. All patients died within a range of 0.2 to 5.3 months (median survival = 2.2 months) from starting radiation therapy. In contrast, 3 of 5 patients (60%) with NHL outside the CNS responded completely and 1 responded partially to involved-field irradiation. These patients survived a median of 12.6 months with one achieving long-term lymphoma-free survival at 40 months. This long-term survivor presented with Stage IE lymphoma as his only manifestation of AIDS. We conclude that AIDS-related lymphomas respond less favorably to radiation therapy than lymphomas in non-immunosuppressed patients. Furthermore, CNS lymphomatous involvement is an ominous occurrence in the AIDS patient. In our experience, cranial irradiation failed to provide significant palliation or survival prolongation in this group of patients. Instead, long-term survival is possible in AIDS patients with limited NHL outside the CNS, and it is in these patients that combination chemotherapy plus involved-field radiation therapy may play a curative role.