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© 2000 American Society for Clinical Oncology Angiocentric Lymphoma of the Head and Neck: Patterns of Systemic Failure After Radiation TreatmentFrom the Departments of Radiation Oncology, Pathology, Internal Medicine, and Otorhinolaryngology, Yonsei University College of Medicine, Yonsei Cancer Center, Seoul, Korea. Address reprint requests to Gwi Eon Kim, MD, Department of Radiation Oncology, Yonsei University College of Medicine, Yonsei Cancer Center, CPO Box 8044, Seoul 120-752, Korea; email therapy@ yumc.yonsei.ac.kr.
PURPOSE: To investigate the patterns of systemic failure and the clinical outcome in patients with angiocentric lymphoma of the head and neck who were treated with radiation alone, and to discuss the optimal mode of treatment for these patients. PATIENTS AND METHODS: We reviewed the records of 92 patients with stage I or II angiocentric lymphoma who were treated at Yonsei Cancer Center between 1976 and 1994. All patients were treated with involved-field irradiation. Radiation doses ranged from 40 to 60 Gy (median dose, 50.4 Gy). Treatment response, patterns of treatment failure including systemic failure, and clinical outcome after radiation treatment were analyzed. RESULTS: The most frequently involved site was the nasal cavity, either alone or in conjunction with other sites. In 16 patients (17.4%), angiocentric lymphoma was accompanied by cervical lymphadenopathy. Disease was classified as stage I in 62 patients (67.4%) and stage II in 30 patients (32.6%). After completion of radiation treatment, 61 patients (66.3%) achieved a complete response and 16 (17.4%) a partial response. Half of the patients (50.0%) ultimately experienced local recurrence with or without other components of failure, whereas regional failure was relatively uncommon (10.9%). Systemic failure occurred in 25.0% of patients during follow-up. Six patients had histologic findings identical to those at the time of the original disease (group I), whereas four patients exhibited morphologic features of frank lymphomas (group II). The majority of patients with systemic relapse had the predilection sites for widespread extranodal involvement, such as the skin, brain, lung, gastrointestinal tract, or testes. In addition, seven patients died from various medical illnesses or immunologic disorders, including hemophagocytic syndrome and second primary cancers (group III). After a median follow-up of 56 months, the overall survival and disease-free survival rates for all patients were 40.1% and 37.8%, respectively. All patients except one with systemic failure died within 1 year. CONCLUSION: Treatment with radiation alone had suboptimal results, partly because of the occurrence of a variety of systemic failure with diverse clinicopathologic features. Given the frequent occurrence of systemic failure after radiation treatment, we believe that the multimodality treatment approach containing more effective chemotherapeutic agents should be incorporated in the treatment of angiocentric lymphoma confined to the head and neck.
ANGIOCENTRIC LYMPHOMA, formerly referred to as polymorphic reticulosis1,2 and midline malignant reticulosis,3,4 is a disorder with protean clinical features and characterized by destruction of the upper respiratory tract, particularly the nasal cavity, palate, and paranasal sinuses.1-6 Pathologically, in most lesions there are angiocentric and angiodestructive patterns, marked necrosis, and infiltration of atypical lymphoid cells. These histologic features are known to resemble closely those of pulmonary lymphomatoid granulomatosis,7-9 but recent studies suggest that some pulmonary cases may be associated with B-cell proliferation. Jaffe et al10 proposed the term angiocentric immunoproliferative lesions to include a broad spectrum of lymphoproliferative disorders, ranging from low-grade lesions of uncertain histogenesis to high-grade angiocentric lymphomas. In the past, it was postulated that infectious and immune mechanisms played roles in the pathogenesis of the disease,3,11 but there is now plentiful evidence to support the lymphomatous nature of the disease process.1,5,6,9,10,12-14 Several immunohistochemical studies have demonstrated that infiltrating cells of angiocentric lymphoma more often express a mature T-cell phenotype.5,10,12,15 However, in some cases, immunophenotypic analysis has revealed peculiar features such as a lack of T-cell antigen and expression of natural-killer (NK) cell–related markers, including an absence of a clonal arrangement of T-cell receptors in the molecular genetic analysis. Although in the Revised European-American Lymphoma classification proposed by the International Lymphoma Study Group, angiocentric lymphoma is categorized as one of the peripheral T-cell and NK cell neoplasms,16 Jaffe et al,17 in the report of the Hong Kong Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas, stated that nasal T/NK cell lymphoma should be considered a distinct clincopathologic entity on the basis of biologic behavior; the characteristic immunophenotype with the expression of CD56+, CD2+, and CD3-; and the strong association with Epstein-Barr virus (EBV). The optimal mode of treatment has also not been decided on, probably because of the rarity of the tumor and limited understanding of its natural course. Several investigators have considered local irradiation to be the preferred treatment for the disease, because of the tendency of the disease to be confined to the midfacial areas and the excellent response to radiation.18-21 Others have questioned the role of radiation treatment, because those patients treated with radiation alone had relatively unfavorable prognoses because of the frequent occurrence of systemic progression. Itami et al22 and Aviles et al23 stated that a combination of radiation and chemotherapy or chemotherapy alone should be considered the primary therapeutic approach. It is now well recognized that such lesions are not always restricted to the upper respiratory tracts, even though uncontrolled local disease or local relapse remains a major cause of death. Moreover, there is a tendency among such lesions toward wide dissemination to nodal or extranodal sites or progression to systemic lymphoma.2,13,18,22 Occasionally, some patients have had various medical illnesses or second malignancies, which might or might not have been related to angiocentric lymphoma.7,11,20 Although a vast amount of research has been conducted in recent decades, most studies have had a pathologic focus; among them are immunohistochemical studies and/or genotypic analysis6,9,10,12,13,15,24 and histogenetic studies about the role of EBV in angiocentric lymphoma.25-28 Only a few reports have included information about tumor behavior,8,12,13,19 but these studies involved a limited number of patients who were treated with a wide range of modalities. Furthermore, the detailed patterns of systemic failure have not been evaluated in an orderly fashion. For these reasons, we conducted a retrospective study to investigate the natural history of the tumor in a series of patients treated with radiation alone at a single institution. The aim of this study was to define the patterns of systemic failure and the clinical outcome after radiation treatment and to discuss the therapeutic implications for these patients.
Between 1976 and 1994, 129 patients with angiocentric lymphoma of the head and neck were treated at Yonsei Cancer Center in Seoul, Korea. Their pathologic material and medical records were retrospectively reviewed. Six patients with Ann Arbor Conference stage III or IV disease at the time of initial presentation were excluded from this analysis, leaving 123 patients with stage I or II disease confined to the head and neck. Before 1987, our treatment policy for stage I or II disease was to administer involved-field irradiation alone, and afterward these patients received either combination chemotherapy followed by radiation or radiation alone, according to the physician’s judgment. The types and schedules of systemic chemotherapy used varied for each patient. Therefore, 31 patients who underwent combined treatment with systemic chemotherapy and radiotherapy were also excluded from the study, so that we could specifically evaluate the results of radiation alone. The study then included 92 patients with angiocentric lymphoma confined to the head and neck who were initially treated with radiation alone. In the case of each patient, a head-and-neck computed tomographic (CT) scan was performed for accurate evaluation of the primary lesion. The other staging evaluation included a complete history and physical examination, a chest x-ray, and laboratory studies including a complete blood count and liver function tests. Liver ultrasound images and whole-body bone scans were obtained. Lymphangiography was performed in earlier cases, but abdominopelvic CT was performed instead of lymphangiography in the majority of patients. Patient characteristics are listed in Table 1. The male-to-female ratio was about 6:4. Median age at the time of initial presentation was 45 years (range, 14 to 76 years). The nasal cavity, either alone or in conjunction with other sites, was the most common site of involvement at the time of presentation. Twenty-four percent of the patients had involvement of two or more anatomic sites of the upper respiratory tract, including the paranasal sinuses, Waldeyer’s throat ring, oral cavity, soft palate, and laryngopharynx. Sixteen cases (17.4%) were accompanied by cervical lymphadenopathy. Disease was classified as stage I in 62 patients (67.4%) and stage II in 30 patients (32.6%). Systemic B symptoms were present in only eight patients (8.7%).
The diagnostic criteria for our patients were strictly morphologic, based on the microscopic findings, although immunohistochemical studies and EBV RNA in situ hybridization were performed in 15 cases late in the study period. The major findings used to identify angiocentric lymphoma were the pathologic features of angiocentric infiltration or an angiodestructive growth pattern and necrosis with polymorphism of individual cells and a variable percentage of atypical lymphoid cells (Fig 1). Pathologic slides for all patients except 12 were rereviewed and reclassified by an experienced special pathologist (W.I.Y.) who was unaware of the patients’ clinical courses. In the case of 12 patients whose pathologic material was either unavailable or inadequate for analysis, we obtained the information from pathologic description in the initial reports. Of the 15 patients in whom immunophenotypic analysis was performed, 12 patients (80.0%) were considered to have T/NK cell lymphoma and three (20.0%) were considered to have T-cell lymphoma. Positive signals for EBV were noted in almost all our patients. Details of immunophenotypic analysis and EBV studies for the 15 patients in whom immunophenotypic analysis was performed are given elsewhere.26
Radiation was delivered using a Co-60 or 4-MeV linear accelerator in daily fractions of 1.8 to 2.0 Gy, 5 days a week, for a total dose of 40 to 50.4 Gy over 4 to 5 weeks, with provision for additional doses of up to 54 to 60 Gy in cases of persistent tumor. Generally, the radiation fields for the primary lesion included the involved area with adequate margins. The radiation ports for the lymph node–bearing area varied according to the primary sites. If the primary lesion was located in the nasal cavity or paranasal sinuses, regional lymph node areas were not included unless they were clinically involved. If the primary lesion was in the Waldeyer’s throat ring or hypopharynx, elective neck irradiation was performed, regardless of neck node involvement. Response to radiation treatment was assessed by physical examination and CT and/or magnetic resonance imaging performed within 6 weeks after the completion of radiation treatment. Tumor response to radiation was assessed using standard criteria. A complete response (CR) was defined as complete disappearance of all assessable disease, and a partial response was defined as more than 50% regression of all assessable disease. Patients with less than 50% clinical regression, stable disease, or disease progression were considered to have no response (NR). All patients were regularly followed at 3-month intervals until death or relapse. Relapse was defined as reappearance of the primary tumor and the existence of other clinical, radiologic, or laboratory evidence of active disease. The salvage treatments for initial relapse were individualized for each patient. Overall survival and relapse-free survival were generated using Kaplan-Meier methods and the differences were evaluated using the log-rank test. Survival time was measured from the date of diagnosis to the date of death or the last follow-up, whereas disease-free survival (DFS) was estimated from the date of treatment to the date of initial relapse. The survival time for all patients with systemic failure was estimated from the date of detection of systemic failure.
Response to Radiation Treatment Objective tumor response to radiation was assessed by clinical and/or radiologic studies within 6 weeks after completion of radiotherapy. Generally, the initial response to radiation treatment was rapid and dramatic. Sixty-one patients (66.3%) achieved a CR and 16 patients (17.4%) achieved a partial response, for an overall response rate of 84%. The remaining 15 patients (16.3%) had NR to radiation. Five patients who did not complete the radiation treatment and/or died from progressive disease during or immediately after radiation treatment were included in the NR category. The initial CR rate for stage I disease was 67.8%, whereas that for stage II disease was 60%, but the difference did not reach statistical significance (P > .05). In addition, there was no significant difference in CR rates between patients with and those without systemic B symptoms (66.7% v 62.5%) (P > .05). Fourteen of the 61 patients who initially achieved a CR experienced subsequent local recurrence from 3 to 77 months (median, 8 months) after treatment.
Patterns of Treatment Failure
Systemic Failure The patterns of systemic failure in 23 patients were notably heterogeneous, with diverse clinicopathologic features. Therefore, we arbitrarily divided these patients into three groups on the basis of the histologic features of the relapse lesions with the exception of six patients whose pathologic diagnosis was not made. When the histologic findings of relapse lesions were compared with those of the original biopsy specimens, six patients were discovered to have the same histologic findings as those of the original tumors (group I). The disseminated lesions in extranodal sites exhibited polymorphic patterns, were accompanied by necrosis and angioinvasion, and were histologically identical to the original infiltrate in the head and neck. However, the appearance of the disseminated lesions was not always polymorphic but was rather monomorphic in a few patients. Of the 23 patients with systemic failure, four patients demonstrated histologic progression to the monomorphic patterns compatible with frank lymphoma at distant sites (group II). In all patients except one in group II, the systemic lesions were diagnosed as diffuse large-cell lymphoma. In patient no. 10, a cutaneous infiltrate was proven to be T-cell lymphoma, immunoblastic type. The majority of patients with systemic relapse in group I and group II had the predilection sites for widespread extranodal involvement, such as skin, brain, lung, gastrointestinal tract, or testes. Seven patients developed secondary neoplasms or other medical diseases during the course of the disease (group III). In three of these patients, adenocarcinomas of the stomach, pancreas, and breast developed 2, 3, and 94 months after radiation treatment, respectively. All three patients underwent radical surgery for their tumors, but they all soon died from second primary cancer. In addition, two patients had histories of uterine cervical cancer and colon cancer, 5 and 10 years before diagnosis of angiocentric lymphoma, respectively. The remaining four patients in group III had had various medical illnesses or immunologic disorders. Three patients developed hemophagocytic syndromes. The diagnosis of hemophagocytic syndrome was made by clinical background and bone marrow study. The diagnostic criteria we adopted included unexplained pancytopenia involving at least two hematopoietic series and readily identifiable hemophagocytic histiocytes in bone marrow examination (> 2% of all marrow nucleated cells) in combination with fever and other clinical features such as hepatosplenomegaly and coagulopathy. Another patient (patient no. 17) died from septicemia accompanied by pancytopenia. We were unable to obtain pathologic material from six patients, because of poor general condition due to widely disseminated disease or because of patient refusal (group IV). All patients in group IV were observed until death, but no autopsies were performed. Involvement of the CNS was the cause of death in patient no. 18, in whom palliative whole-brain irradiation was performed. This patient had a normal finding on brain CT, despite paresis of the multiple cranial nerves, which was interpreted as invasion of the skull base. Three patients had hepatic involvement as demonstrated by abdominal CT, showing scattered, multiple space-occupying lesions. One of them (patient no. 19) had involvement of multiple sites. On the other hand, two patients developed nodal relapse in the mediastinal lymph node (patient no. 22) and axillary lymph nodes (patient no. 23). The primary lesion of the nasopharynx in patient no. 23 responded poorly to radiation, and involvement of the bilateral axillary lymph nodes and hepatomegaly were noted during radiotherapy. These systemic lesions were apparently refractory to systemic chemotherapy and even progressed during salvage chemotherapy. Relevant examples of each group are summarized in Table 2.
Risk Factors Predictive of Systemic Failure Several parameters such as age, sex, location of tumors, number of tumors, lymph node involvement, Ann Arbor Conference stage, systemic B symptoms, and response to radiation were investigated to define the subgroups of patients at a higher risk for systemic failure. On univariate analysis, age and sex were not identified as statistically significant determinants of systemic failure. The location of the primary tumor, multiplicity of the lesion, and lymph node involvement also were not high risk factors. As expected, the incidence of systemic failure was much higher in patients with stage II disease than in patients with stage I disease (36.7% v 19.4%), but the difference was not statistically significant (P > .05). In addition, the incidence of systemic failure in patients with systemic B symptoms was higher than that in patients without systemic B symptoms (50.0% v 22.5%), but again the difference was not statistically significant (P > .05). The influence of various factors potentially affecting the development of systemic failure at the time of initial presentation is summarized in Table 3.
Survival of Patients With Systemic Failure The 92 patients who were treated with radiation alone had relatively unfavorable prognoses. Overall 5-year actuarial survival and DFS rates for all patients were 40.1% and 37.8%, respectively (Fig 4). On univariate analysis, the Ann Arbor Conference stage and response to radiation treatment were found to be significant prognostic factors for overall survival and DFS, but age, sex, number of tumors, lymph node involvement, and presence of systemic B symptoms had no impact on survival. The 5-year actuarial survival rate for patients with stage I disease was 64.4% and that for patients with stage II disease was 25.2% (P < .1), whereas the 5-year DFS rate for patients with stage I and those with stage II disease were 47.6% and 15.2%, respectively (P < .01). In addition, the treatment results were sharply divided between the CR group and the non-CR group. The 5-year survival rate for the 61 patients who achieved a CR after radiation treatment was 61.5%, whereas none of the patients who did not obtain a CR survived for 5 years (P < .01). However, there was no clear relationship between the presence of systemic B symptoms and treatment outcome.
On the other hand, the 23 patients who subsequently developed systemic failure had extremely grave prognoses (Fig 5). All patients except one with systemic disease died within 1 year, regardless of the underlying pathology of relapse lesions and the type of salvage treatments. Approximately one third of the patients died from disease progression within 3 months. The median survival time after diagnosis of systemic failure was less than 6 months (range, 1 to 14 months). The overall 1-year survival rate for patients with systemic failure was 4.3%. None of the patients survived for more than 2 years. However, there was no significant difference in survival patterns between patients in group I and those in group II. A variety of aggressive salvage treatments were attempted in the majority of patients in both groups, but none were successful. In addition, all three patients who subsequently developed second primary cancers died from cancer progression, despite curative surgery. Moreover, four patients in group III with hemophagocytic syndrome or medical complications had the worst survival. All patients with such medical illness had a rapid, fatal clinical course over a few weeks.
In this study, we attempted to identify the patterns of systemic failure and treatment outcome in patients with angiocentric lymphoma, in an effort to recommend the optimal mode of treatment. Our patients with stage I or II head and neck angiocentric lymphoma who were treated with radiation alone had relatively unfavorable prognoses, partly because of the evolution of a variety of systemic failure in a significant portion of patients. Additionally, our findings confirmed those of previous investigations2,13,22,29 in which the patterns of systemic failure were notably heterogeneous, with diverse clinicopathologic features. We arbitrarily divided patients with a broad clinical spectrum of systemic failure into three categories, with the exception of patients whose pathologic diagnoses were not available. Generally, the initial response to radiotherapy was rapid and dramatic in our patients, as in previous studies.18-21 Despite a relatively favorable response to radiation, local recurrence was the most frequent site of failure and remained the principal obstacle to successful treatment. The vast majority of local recurrence occurred at or around the original tumor volume, although a few local failures occurred elsewhere outside the irradiated fields of the head and neck. Exactly one half of our patients ultimately experienced local failure. By contrast, lymph node involvement was far less common initially or during the disease course. Of the 92 patients with angiocentric lymphoma confined to the head and neck, only 17% were found to have regional neck disease on initial presentation, and less than 10% had subsequent development of nodal relapse at the ipsilateral neck or supraclavicular node. Node involvement outside the neck was quite uncommon. Only four patients relapsed at the mediastinal lymph nodes or axillary lymph nodes during the follow-up periods, but no patients, even patients with widely disseminated disease, relapsed at the subdiaphragmatic nodes. It is evident from our experience as well as from other reports13,22,23 that the disease process can be either confined to the head and neck or widely disseminated to the nodal or extranodal sites. Although it is unclear whether this represents metastases of a neoplastic component from the primary lesion or a manifestation of multifocal neoplasia itself,4 approximately 25% of our patients exhibited a variety of systemic failure during the disease course. The histologic findings of disseminated lesions did not always show the polymorphic patterns and necrosis and angioinvasion that had been observed at the time of the initial diagnosis. The morphologic characteristics of the disseminated lesions were variable, from the same features as the original infiltrates to findings corresponding with frank lymphomas. On occasion, they displayed the patterns with monomorphic sheets of typical lymphoid cells that were histologically interpreted as true T-cell lymphoma. However, it is unclear whether the polymorphic patterns of the primary lesion transform to monomorphic patterns with a more malignant behavior or whether the two situations represent a single clinicopathologic entity with varying degrees of clinical aggressiveness. Although some authors have suggested that previous treatments such as steroid medication or radiation treatment may influence histopathologic features,1,2 the majority of recent data support the concept that both are regarded as a spectrum of malignant lymphoma of T-cell lineage related to the angiocentric immunoproliferative lesion.10,29,30 In the majority of our patients with widespread dissemination, there was a tendency toward extranodal involvement of sites such as the lungs, liver, or gastrointestinal tract. More widespread involvement, including spread to unusual sites such as the testes or skin, were occasionally observed. However, it is debatable whether a tendency toward spread to such sites is unique to angiocentric lymphoma. More recent studies have found that there is a specific range of involvement in angiocentric lymphoma, particularly nasal-type T/NK cell lymphoma.17,31-33 Kern et al stated that peripheral T-cell lymphoma with expression of a NK cell marker, the neural cell adhesion molecule, exhibited a tendency to involve certain extranodal sites such as the CNS, skin, and gastrointestinal tract. This was explained by homophilic binding properties, the homing and migration of lymphoma cells to these organs, which are rich in neural cell adhesion molecule–positive nerve endings. Other investigators have also agreed that the tendency toward dissemination to particular locations such as the gastrointestinal tract, skin, or testes is an intriguing phenomenon in nasal-type T/NK cell lymphoma,31,32 but we were unable to investigate such correlations because the immunophenotypic studies of pathologic materials were recently performed in only a small number of our patients. Because our patients were chosen on the basis of having angiocentric infiltration and necrosis, it is likely that most of our patients would have T/NK cell or T-cell lymphomas. In fact, patients with T/NK cell lymphomas, unlike those with T-cell lymphomas, often have characteristic clinical courses with frequent extranodal presentations, aggressive disease, and poorer prognoses. Therefore, this study has an inherent flaw in that our patients had T-cell or T/NK cell lymphoma involving the head and neck; these lymphomas may have different natural histories, respond differently to radiation, and have different patterns of systemic failure. Angiocentric lymphoma was closely linked to a variety of medical complications or immunologic disorders. It has been suggested that angiocentric lymphomas occasionally retain immunologic dysfunction, which may be reflected in some clinical manifestations observed in patients with T-cell malignancies. Ishii et al34 and Sordillo et al11 found profound immunologic deficit in a few patients with angiocentric lymphomas, probably resulting from the impairment of T-lymphocyte function. Medeiros et al29 also supported the opinion that patients with angiocentric lymphoma could express the underlying immune deficiency, presumably associated with EBV, that occurred in immunosuppressed patients such as patients who have undergone transplantation. Three patients in our series had had hemophagocytic syndromes that occurred at any time during the clinical course and usually were quickly fatal, over several weeks. These complications are likely mediated by cytokines released by T-lymphoma cells that are related to EBV.35,36 In addition, a few of our patients died from septicemia or intractable hemorrhage, usually in conjunction with neutropenia or thrombocytopenia. However, it is unclear whether the high association of angiocentric lymphoma with such medical complications is a chance observation or whether it reflects a distinct pattern of disease related to the immunologic deficit. On the other hand, some of our patients developed new primary cancers during the follow-up period. The most striking clinical outcome in such patients was the rapid progress of a new primary cancer after diagnosis. Regardless of aggressive treatments for second primary cancers, most of them died from rapid progression of cancers within 1 year. However, only limited information is now available regarding the relationship between angiocentric lymphoma and the evolution of new primary cancers. In an earlier study of 10 patients with midline granuloma by Fauci et al,37 in which three patients developed second primary cancers, the authors speculated that such patients with aberrant immunologic reactions would have an increased propensity for development of new cancers. Until recently, there was no clear consensus on optimal management for the disease, probably because of the rarity of the tumor and little understanding of its natural history. Notwithstanding the inconsistent response to radiation, radiation treatment is still accepted as the treatment of choice for the localized form of angiocentric lymphoma,18-21 and a CR after radiation treatment is still the most important determinant of favorable survival.2,19 However, it seems more logical that systemic therapy should be included as a part of the treatment program, even for patients with a lesion apparently confined to the head and neck, given frequent systemic relapse after radiation treatment alone. Nevertheless, several investigators have questioned the efficacy of chemotherapy.20,21,38 Although scattered studies indicated that systemic chemotherapy produced a favorable response and possibly affected survival,22,30 angiocentric T-cell lymphoma has been generally known to be refractory to conventional combination chemotherapy similar to the regimens used in malignant B-cell lymphoma. Yamaguchi et al emphasized that the poorer response of patients with angiocentric lymphoma treated with chemotherapy may result from frequent expression of the multidrug resistance gene (P-glycoprotein/MDR1). In addition, it seems doubtful that cytotoxic chemotherapy can be expected to reduce the risk of second primary cancers and to ameliorate intractable hemorrhage, sepsis, or hemophagocytic syndrome, which all adversely affect survival. Sobrevilla-Carvo et al and Grange et al39 wondered whether initial chemotherapy carried a high risk of bleeding and septic complications, particularly in patients with leukopenia induced by combination chemotherapy. Therefore, we believe that the development of an effective combination of new drugs for this disease is urgent, even though the addition of systemic treatment may be required for such patients. Moreover, future studies should identify the subgroup of patients who would benefit from additional systemic treatment. In summary, we demonstrated a broad clinical spectrum of disease in patients with angiocentric lymphoma who were treated with radiation alone. Although local failure was a major obstacle to successful treatment, a significant portion of patients had a variety of systemic failure that was notably heterogeneous, with diverse clinicopathologic features. The optimal treatment for these patients remains undetermined, but treatment with radiation alone has suboptimal results, despite a relatively favorable response. Given the frequent occurrence of systemic failure after radiation treatment, we believe that the multimodality treatment approach containing more effective chemotherapeutic agents should be incorporated in the treatment of angiocentric lymphoma confined to head and neck. However, a prospective randomized study should be conducted, to determine whether a systemic approach will have an impact on the natural history of the disease.
Supported in part by grant no. 986-0700-006-2 from the Korean Science and Engineering Foundation under the program of the Korean-Japan Joint Committee for Basic Scientific Research.
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Copyright © 2000 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
