Consolidation radiotherapy following brief chemotherapy for localized diffuse large B-cell lymphoma: a prospective study

Many physicians administer involved field radiation therapy (RT) following brief chemotherapy for localized aggressive non-Hodgkin's lymphoma. Involved field irradiation usually implies treatment to the involved nodal regions with and without the contiguous lymphatic region, however, there is no agreements about its definition. Here we assess the appropriateness of RT irrespective of lymph node regions (localized field) following chemotherapy for patients with early stage diffuse large B-cell lymphoma. The localized field encompassed all original gross tumor volumes before chemotherapy with at least a 2- to 3-cm margin irrespective of lymphatic regions. We also evaluated the suitable radiation dose on the basis of response to chemotherapy. Twenty five eligible patients were treated with 3 cycles of chemotherapy (CHOP) followed by RT. All 25 patients had disease confined to Waldeyer's ring and/or cervical lymph nodes. Twenty two patients in complete response following chemotherapy received 30 Gy, and the remaining 3 in partial response received 40 Gy. With a median follow up of 42 months, both event free and overall survival rates at 2 years were 96.0%. There were no in-field recurrences, however, two patients experienced relapses. One developed central nervous system involvement and subsequently died of his disease. The other had mediastinal and submental lymph node relapse at 32 months, and is alive after salvage chemotherapy. Our study demonstrated that it should be possible to reduce treatment volume to less than the conventional involved field, and to limit the dose of RT in the range of 30-40 Gy.     

Lymphoma of the breast in Hong Kong Chinese

Fourteen cases of non-Hodgkin's lymphoma presenting as breast mass from 1974 to 1996 were reviewed. The median age of presentation was 51 years. Three patients had bilateral disease and five had disseminated disease. A predominance of B cell disease of diffuse large cell histology was noted. Painless lumps were the most common presenting features and most patients were treated with excisional biopsy followed by combination chemotherapy. Radiotherapy was added to local bulky disease. Six patients, however, underwent mastectomy. The overall CR rate was 74 per cent, lasting a median of 32 months. At a median follow-up of 60 months five patients were still alive, one with relapsed disease. Salvage treatments for relapsed patients were uniformly poor. Compared to reported western series, our patients had more high grade disease, more T cell disease and more CNS relapses. Improvements in treatment may involve the use of fine needle aspiration of breast lesion prior to surgery, primary CNS prophylaxis in high grade disseminated disease and high dose chemotherapy with marrow/stem cell rescue in relapsed cases. © 1997 John Wiley & Sons, Ltd.     

Primary paranasal sinus lymphoma: natural history and improved outcome with central nervous system chemoprophylaxis

Non-Hodgkin's lymphoma of the paranasal sinus is an uncommon presentation of extranodal lymphoma. Its natural history, treatment and prognosis have been infrequently characterized in the medical literature; however, a tendency to involve the central nervous system (CNS) has been noted. In British Columbia (population 4 million), a central database for lymphomas has allowed us to accurately track cases of paranasal sinus lymphoma diagnosed since 1980. A retrospective review was performed on the 44 patients who presented with primary paranasal sinus lymphoma (stage I or II) between 1980 and 1999. Histologic features were identified and immunophenotypic classification performed. Complete diagnostic and follow-up data including stage, treatment, response rates, sites of relapse and survival data were available for all patients. There were 26 men and 18 women. The types of lymphoma found were: diffuse large B cell (including immunoblastic), n = 37 (84%); T/NK nasal type, n = 3 (8%); peripheral T cell, not otherwise classified, n = 2 (4%); and others, n = 2 (4%). The median age at presentation was 66 years (range 27-97 years). The median follow-up for living patients was 114 months. For all 44 patients, the 5- and 10-year overall survivals were 48% and 41% and the disease-specific survivals 62% and 62%, respectively. Beginning in May 1985, intrathecal chemotherapy was added to our standard treatment plan of multi-agent chemotherapy and local irradiation. Before 1985, 2 of 5 patients developed leptomeningeal metastasis. Following the institution of intrathecal chemotherapy, only 8% (3 of 39) of patients have developed CNS disease. Introduction of intrathecal chemoprophylaxis was also associated with an improvement in overall survival from 20% to 51% and disease-specific survival from 40% to 65%. Primary paranasal sinus lymphoma is an uncommon presentation of lymphoma that carries the potential risk of spreading to the leptomeninges. Treatment with combined modality chemotherapy and irradiation can cure many patients and the addition of intrathecal chemotherapy may reduce the risk of CNS relapse.     

Primary mediastinal large B-cell lymphoma: results of intensive chemotherapy regimens (MACOP-B/VACOP-B) plus involved field radiotherapy on 53 patients. A single institution experience

PURPOSE: The optimal therapy for primary mediastinal large B-cell lymphoma (PMLBCL) remains undefined. The superiority of intensive chemotherapy regimens (Methotrexate, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, Bleomycin [MACOP-B]/Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone, Bleomycin [VACOP-B]) over Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP)-like chemotherapy is upheld by some authors. The role of radiotherapy is still debated. In the absence of randomized trials, we report clinical findings and treatment response in 53 consecutive patients treated with intensive chemotherapy and mediastinal involved-field radiation therapy (IFRT). METHODS AND MATERIAL: Fifty-three consecutive patients with PMLBCL were retrospectively analyzed. Planned treatment consisted of induction chemotherapy (I-CT; Prednisone, Methotrexate, Doxorubicin, Cyclophosphamide, Etoposide-Mechloroethamine, Vincristine, Procarbazine, Prednisone [ProMACE-MOPP] in the first 2 patients, MACOP-B in the next 11, and VACOP-B in the last 40) followed by IFRT. Planned treatment was concluded in 43 of 53 patients; in 10 patients, I-CT was not immediately followed by IFRT. Among these 10 patients, 6 received high-dose chemotherapy (HD-CT) followed by IFRT, 2 received HD-CT, and 2 received no further treatment. RESULTS: After a median follow-up of 93.9 months (range, 6-195 months), 45 of 53 patients (84.9%) were alive without disease. Eight patients died: 7 of PMLBCL and 1 of toxicity during HD-CT. The 5-year disease-free survival (DFS) and overall survival rates were 93.42% and 86.6%, respectively. The response rates after I-CT were complete response (CR) in 20 (37.73%) and partial response (PR) in 30 (56.60%); 3 patients (5.66%) were considered nonresponders. Among patients in PR after chemotherapy, 92% obtained a CR after IFRT. CONCLUSIONS: Our report confirms the efficacy of intensive chemotherapy plus mediastinal IFRT. IFRT plays a pivotal role in inducing CR in patients in PR after chemotherapy.     

Primary breast lymphoma

Primary breast lymphoma (PBL) is a rare form of localized extranodal lymphoma. Few reports are available in the literature concerning its treatment and outcome. Of the 34 cases of PBL seen at our institution over a 25-year period, 20 consecutive cases were treated with CHOP or CHOP-like chemotherapy regimen and had adequate biopsy specimens for histological review. All these 20 PBL were of B-cell origin including one case of Burkitt lymphoma, and 2 cases of low-grade histologic type. Sixteen of the 20 patients achieved a complete remission (CR) and 2 achieved a partial remission (PR) (>75% tumor regression). Two patients had progressive disease while on therapy. With a median follow-up period of 80 months, 6 patients relapsed. Median time to relapse from diagnosis was 23 months (range, 3-41 months). Two of the relapses involved the central nervous system (CNS): isolated CNS relapse in one case and associated with other relapse sites in 1 case. The two patients who achieved a PR after chemotherapy also had disease progression to the CNS, 4 and 8 months after the end of CHOP chemotherapy. All 4 patients died of their disease 3, 6, 10 and 13 months after CNS involvement. Of the 16 centroblastic diffuse large B-cell lymphoma (DLCL), 3 had CNS disease at relapse. Three (15%) of our study patients developed a controlateral breast relapse. Twelve of the initial 20 patients were alive, including 11 with a persistent CR, 6 patients died of their lymphoma and 2 of unrelated diseases. In conclusion, we observed a high incidence of CNS relapse in this group of localized extranodal lymphoma, strongly suggesting that CNS prophylaxis should be associated with systemic chemotherapy in localized PLB.     

14例原发性鼻窦非霍奇金淋巴瘤的临床分析

背景与目的:原发性鼻窦非霍奇金淋巴瘤(primary paranasal sinus lymphoma,PPSL)临床上较罕见,其生物学行为较独特.本文总结和分析PPSL的临床病理特点和治疗情况,以期增加对此病的认识.方法:回顾性分析1994～2006年中山大学肿瘤防治中心收治的14例PPSL,分析其临床和病理特点、治疗经过和随访结果.结果:14例中原发于上颌窦者11例,筛窦2例,蝶窦1例.根据淋巴瘤Ann Arbor分期,所有患者均为Ⅰ～Ⅱ期.根据美国癌症联合委员会(AJCC)的鼻窦实体瘤TNM分期标准,大部分患者(11/14)属于局部晚期T3～T4.病理类型:B细胞性12例(85.7%),其中弥漫大B细胞性占42.9%(6例);T细胞性1例,非B非T细胞性1例.2例接受上颌窦根治术,12例为肿物切除或活检;14例全部接受化疗,6例化疗后接受局部放疗.中位生存期59.5个月,全组5年总生存率和无事件生存率均为78.6%.结论:PPSL发病部位以上颌窦多见,病理类型以B细胞性为主,其中弥漫大B细胞性最常见,肿瘤局部侵犯广泛为其重要特征;采用全身化疗和局部放疗联合治疗,患者总体预后相对较好.     

Favorable Outcome After Adjuvant Involved-Field Radiotherapy After Autologous Hematopoietic Stem-Cell Transplantation in Patients With High-Risk Relapsed/Refractory Lymphoma: A Single-Center Experience

BackgroundPatients with refractory or relapsed lymphoma diagnosed with bulky disease at relapse or with residual disease after salvage treatment are considered to have a dismal outcome, even after autologous hematopoietic stem-cell transplantation, as a result of disease recurrence. To minimize the risk of relapse after receipt of a transplant, involved-field radiotherapy (IFRT) to sites of either bulky or localized residual disease has been utilized; however, the ideal timing for irradiation remains controversial. The aim of this study was to assess the safety and efficacy of IFRT in the early period after transplantation.Patients and MethodsWe retrospectively evaluated the outcome of 24 autografted patients with relapsed/refractory lymphoma who presented with bulky disease at relapse or who had a persistent localized residual mass after salvage treatment and consolidated with IFRT within 4 months after autografting.ResultsNo significant toxicity was noticed during the early postradiotherapy period, while graft function was not impaired. After a median follow-up of 3 years for survivors, 21 patients were alive, 19 of whom were event free, while 2 patients died of disease recurrence and 1 died of treatment-related myelodysplastic syndrome. The 3-year overall, lymphoma relapse-free, and event-free survival rates were 86%, 86%, and 82%, respectively.ConclusionTaking into consideration the poor-risk features of the study cohort, IFRT provided early after autologous hematopoietic stem-cell transplantation showed a safe and well-tolerated toxicity profile and demonstrated long-term effective tumor control, as reflected in the promising survival rates.     

Is central nervous system prophylaxis necessary in ocular adnexal lymphoma?

PURPOSE: To examine the frequency of metastasis to the eye and central nervous system (CNS) from ocular adnexal lymphomas and to evaluate whether CNS prophylaxis is appropriate for these tumors. PATIENTS AND METHODS: Seventy-one patients with biopsy-confirmed ocular adnexal lymphomas were evaluated between 1989 and 1995. The lymphomas were subclassified histopathologically according to the new Revised European-American Lymphoma (REAL) criteria. Molecular genetic analysis of tumor cell DNA was done by Southern blot. Patients had a complete ophthalmologic evaluation and metastatic work-up and were then routinely followed up by an ophthalmologist and a medical oncologist. RESULTS: The 34 men and 37 women studied had a median age of 67 years (23 to 92). Ocular adnexal lymphomas were situated in the orbit in 54 patients, in the conjunctiva in 14 patients, and in the eyelid in 3 patients. Bilateral involvement occurred in 11 patients. The most common histologic diagnoses were (54 patients, 76%) extra-nodal marginal zone lymphomas and small lymphocytic lymphomas in 10 patients (14%). Molecular genetic analysis performed in all patients confirmed a monoclonal B-cell population in 55 patients (77%), including a single rearrangement of the immunoglobulin heavy chain gene in 14 patients, and more than two rearrangements in 41 patients. No patients had isolated T-cell gene rearrangements. Localized ocular adnexal lymphoma was diagnosed in 43 patients (61%), 17 patients (24%) were found to have concurrent extraocular lymphoma on metastatic work-up and 11 patients (15%) had a previous diagnosis of systemic lymphoma before the onset of their ocular tumor. The median duration of follow-up was 20 months. Overall, 32 patients (45%) had tumors, which remained localized to the orbit adnexa. Eleven patients (15%) relapsed, but none had eye or central nervous system involvement nor required CNS-directed therapy. Although eight patients died, only two died as a direct result of systemic lymphoma. No patient received CNS prophylaxis with either intrathecal chemotherapy and/or radiation therapy. CONCLUSION: Ocular adnexal lymphomas are rare non-Hodgkin's B-cell lymphomas. Metastatic involvement of the eye or central nervous system is rare and CNS prophylaxis with radiotherapy or chemotherapy is unnecessary.     

Non-Hodgkin's lymphomas of head and neck extranodal sites

The initial staging, therapy and course of 156 patients with non-Hodgkin's lymphomas of head and neck extranodal sites were analyzed to determine whether they have a natural history which differs from primary nodal disease. The sites involved were: Waldeyer's ring-103 patients (tonsil-60, nasopharynx-25, base of tongue-18), and extralymphatic sites-53 patients (salivary gland-20, paranasal sinus-20, oral cavity-10, and larynx-3). Seventy-six percent had unfavorable histologies and 24% had favorable histologies. Fifty-three percent had pathologic Stages I-II and 47% had Stages III-IV. The 5-year survival was influenced by primary sites: salivary gland-61%, oral cavity-57%, tonsil-49%, base of tongue-47%, nasopharynx-36% and paranasal sinus-12%. The 5-year survival was also influenced by histology: unfavorable histologies-39%, favorable histologies-69%. The Ann Arbor staging system was more useful than TNM for determining outcome. For patients with Stage I-II unfavorable histologies treated with radiation alone, the 5-year survival was: involved field-24%, extended field-42%, total lymphoid irradiation-52%. The majority of patients who failed did so in extranodal sites. Forty-one patients with advanced disease received a variety of chemotherapy regimens as the sole treatment. There was a high percentage of CNS recurrence with paranasal sinus lymphoma, and CNS prophylaxis may be necessary. For head and neck extranodal lymphomas, limited radiation is inadequate, and combined modality programs should be considered.     

Highly effective local control and palliation of mantle cell lymphoma with involved-field radiation therapy (IFRT)

PURPOSE: Although radiosensitivity of mantle cell lymphoma (MCL) has been demonstrated in vitro, radiotherapy is rarely employed in treatment of MCL. We studied clinical responses of MCL patients treated with involved-field radiation therapy (IFRT) predominantly for local control and/or palliation. METHODS AND MATERIALS: A total of 21 consecutive patients (38 sites) treated with IFRT for MCL were retrospectively analyzed. Median age was 68. Seventeen patients had Stage IV/relapsed disease, 1 had Stage II, and 3 had Stage I disease. Most patients received prior chemotherapy, with an average of two combinations per patient. Mean number of sites treated per patient was two. Mean total dose was 30 Gy. RESULTS: Mean follow-up was 13 months. Overall local response rate was 100%. Complete response was obtained in 64% of the sites and partial response in 36%. Average time to response was 20 days. Twenty-eight sites had a response before radiation therapy was complete. Of 16 sites associated with pre-IFRT pain or discomfort, 15 exhibited post-IFRT relief. Thirteen sites (34%) exhibited local progression, with a median time to progression of 10 months, and an average response duration of 9 months. Five patients experienced Grade II radiation-related toxicity. No Grade III toxicity was reported. Twelve-month overall survival for patients receiving IFRT was 55%. CONCLUSIONS: Radiotherapy provided effective and lasting local responses in MCL patients and was associated with minimal toxicity. Radiation doses required for most lesions were relatively low and responses were noticed early in the course of treatment. Radiation therapy should be considered early in the course of relapsing, refractory, or localized MCL.     

Favorable early-stage Hodgkin lymphoma

The category of favorable early-stage Hodgkin lymphoma (HL) includes patients with Ann Arbor stages I or II disease with no bulky disease or B symptoms. The precise definition of favorable versus unfavorable early-stage disease may vary among American and European cooperative groups. The overall 10-year survival rate of patients with favorable early-stage HL exceeds 90%. Indeed, effective treatments for this group of patients have been available for more than 4 decades. However, treatment strategies have radically changed over the past 15 years and focus now on maintaining the high cure rate while reducing the risk of treatment-related long-term morbidity. The optimal treatment is still evolving, and more recently, reduction in the total amount of chemotherapy and in radiation field and dose has shown excellent results. Combined modality therapy is the preferred treatment for patients with classical favorable early-stage HL (nodular sclerosis or mixed cellularity histology). Patients with early-stage lymphocyte predominance HL are highly curable using involved-field radiation therapy (IFRT) alone and do not require chemotherapy. Classical favorable HL is also curable with radiotherapy alone or with chemotherapy alone, but larger fields and higher-dose radiation or longer chemotherapy is required compared with combined modality. The freedom from treatment failure rate is significantly better with a combination of short chemotherapy and IFRT than with either chemotherapy or radiotherapy alone. Although combined modality is the standard preferred treatment for favorable disease, radiation therapy alone or chemotherapy alone could be considered under special circumstances or as part of an investigational protocol.     

Lymphome de Hodgkin: traitement des stades localisés sus-diaphragmatiques

The risk-adapted therapeutic strategy used for adult patients with Hodgkin’s lymphoma is defined taking into account their risk factors and includes standard first-line ABVD chemotherapy. In early-stage supradiaphragmatic disease, 3 chemotherapeutic courses are applied for patients without risk factors while 4 courses are used for patients with risk factors, followed by a radiation therapy targeting initially involved fields (IFRT) at a dose of 30 Gy. Final analysis of the results of recent trials is expected to determine whether IFRT doses may be reduced to 20 Gy in patients showing chemotherapy-induced complete remission. Chemotherapy alone is not recommended currently, except in ongoing clinical trials in which positron emission tomography (PET) scans are used to evaluate the early response to chemotherapy without radiation. Modern radiation and imaging modalities are expected to permit the restriction of radiation-targeted volumes to initially involved nodes only.     

Phase I study of involved-field radiotherapy preceding autologous stem cell transplantation for patients with high-risk lymphoma or Hodgkin's disease

PURPOSE: This Phase I study was designed to evaluate the tolerability of involved-field radiotherapy (IFRT) to areas of persistent disease in patients with high-risk Hodgkin's disease and non-Hodgkin's lymphomas before autologous stem cell transplantation (ASCT). METHODS AND MATERIALS: Thirty-one patients with primary refractory or relapsed Hodgkin's disease (n = 13) and non-Hodgkin's lymphoma (n = 18) were treated with IFRT followed by high-dose chemotherapy and ASCT. All patients had bulky disease (> or =5 cm) and/or an inadequate response to salvage chemotherapy. The IFRT dose was escalated to a maximum of 36 Gy. Dose-limiting toxicity was defined as Grade 3-4 Bearman toxicity (life-threatening/fatal toxicity occurring within 28 days of ASCT). The chemotherapy regimen consisted of cyclophosphamide, etoposide, and carmustine. RESULTS: The delivered dose of IFRT was 20 Gy in 9 patients, 28-30 Gy in 20, and 32-36 Gy in 2 patients to mediastinal (n = 19) and nonmediastinal (n = 12) sites. The median interval between IFRT completion and ASCT was 19 days. One patient developed Bearman Grade 3 hepatic toxicity. No other Grade 3 or 4 Bearman toxicity was observed. An increased requirement for i.v. narcotics was observed in patients treated with mediastinal IFRT vs. nonmediastinal IFRT (p = 0.02). A trend toward increased mucositis severity was seen in patients previously treated with a larger number of chemotherapy agents (p = 0.09) and in those with a shorter interval between IFRT and ASCT (p = 0.12). Pulmonary toxicity was more common in patients treated with mediastinal IFRT than in those treated with nonmediastinal IFRT (21% vs. 0%, p = 0.13). The 2-year overall and progression-free survival rate was 70% and 49% for all patients, 84% and 50% for patients with Hodgkin's disease, and 59% and 47% for patients with non-Hodgkin's lymphoma, respectively. CONCLUSION: The maximal tolerated dose of IFRT was not reached when Grade 3-4 Bearman toxicity was dose limiting. Increased pulmonary toxicity and mucositis severity was seen after mediastinal IFRT compared with nonmediastinal IFRT. Because local control was excellent, higher doses of IFRT are not recommended. The absolute benefit of IFRT in this patient population needs investigation in future studies.     

CHOP followed by involved field radiotherapy for localized primary gastric diffuse large B-cell lymphoma: results of a multi center phase II study and quality of life evaluation

We aimed to define the role of cyclophosphamide, vincristine, doxorubicin, prednisone (CHOP) followed by involved field radiotherapy (IFRT) for treating localized primary gastric diffuse large B-cell lymphoma (DLBCL). Newly diagnosed patients with localized primary gastric DLBCL were to receive four cycles of CHOP followed by IFRT of 40.0 Gy. At 1 year after the completion of treatment, patients filled out the EORTC Quality of Life Questionnaire specified for stomach cancer (QLQ-C30-STO22). Fifty evaluable patients (25 men, 25 women) were included. The median age was 54.5 years (range, 21 - 73 years. The overall response rate to the CHOP was 94% (95% confidence interval [CI], 87 - 100) in the intent-to-treat population. Forty-one of the 50 patients (82%; 95% CI, 71 - 93) achieved complete remission (CR). After the completion of radiotherapy, five patients who were in PR following chemotherapy eventually attained CR. The overall complete response rate was thus 92% (95% confidence interval, 84 - 99). With a median follow-up period of 30 months, the 2-year progression-free and overall survival rate was 92% and 92%, respectively. The gastric function was well preserved with negligible stomach-related symptoms at 1 year after the completion of treatment. This organ-preserving combined treatment is highly effective and well tolerated for the patients with localized gastric DLBCL.     

Recent progress in the treatment of malignant lymphoma

The present state of the art and developments in the treatment for Hodgkin's disease (HD), follicular lymphoma (FL), MALT lymphoma, and aggressive non-Hodgkin's lymphoma are reviewed. Four courses of ABVD therapy (ABVd therapy in Japan) followed by involved-field irradiation (IFRT), and 6 to 8 courses of ABVD (ABVd in Japan) are the current state art of the therapy for early stage HD and advanced stage HD, respectively. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is also the state of the art for refractory or relapsed HD within 1 year after complete remission (CR) produced by polychemotherapy. The prognosis of the patients with 3 or more International Prognostic Scores (IPS) is poor. New intensified polychemotherapy or auto-HSCT as up-front setting is under randomized phase III clinical trial in Europe and the USA. There is no state of the art therapy for indolent lymphoma including FL, or MALT. Promising results were reported from clinical studies using new anti-lymphoma drugs such as rituximab, iibritumomab, or purine analogs (cladribine and fludarabine), and auto-HSCT with effectively purged stem cells or allogeneic HSCT. These therapeutic strategies hold a possibility of cure for indolent lymphomas. Antibiotic treatment for Helicobacter pylori-positive localized gastric MALT lymphoma is the state of the art therapy. However, there is no standard therapy for advanced stage MALT lymphoma. Risk adapted therapy using the International Prognostic Index is essential for the treatment of aggressive NHL. Three courses of CHOP followed by IFRT for localized aggressive NHL and 8 courses of CHOP for the low-risk group of advanced stage aggressive NHL are the state of the art therapies, respectively. High-dose chemotherapy with auto-HSCT is also the state of the art for sensitive relapse patients with aggressive NHL. Although some clinical studies suggested that high-dose chemotherapy with auto-HSCT as up-front setting for high-intermediate or high-risk group aggressive NHL is more effective than conventional chemotherapy, the efficacy remains to be determined. The development of new therapeutic strategies with combined use of molecular targeting drugs such as rituximab, or new anti-lymphoma drugs such as purine analogs, and HSCT is desired for more effective therapy for refractory lymphomas.     

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.     

Primary non-Hodgkin's lymphomas of the paranasal sinuses and nasal cavity. A report of 18 cases with stage IE disease.

During a 26-year period (1961-1987), a total of 18 patients with primary non-Hodgkin's lymphoma (NHL) of the paranasal sinuses and nasal cavity received radiation therapy at (University of California at Los Angeles) UCLA Medical Center. At the time of diagnosis and using the available diagnostic methods, none of these patients had clinically detectable disease beyond the paranasal sinuses. All 18 patients were staged IE by the Ann-Arbor system. When the patients were staged according to the AJC staging system from epithelial tumors, half presented with advanced T3-4 disease. Diffuse histiocytic lymphoma was the most common histology (eight cases) and maxillary sinus, the most common site of origin (11 cases). All nine T1-2 tumors received radiation therapy alone, while radiation and chemotherapy was used in seven of nine advanced T3-4 staged tumors. The mean follow-up was 71 months. At last follow-up, eight of nine T1-2 patients were rendered disease-free. In contrast, only four of nine T3-4 patients had long-term disease-free survival. Seventy-five percent of the failure occurred within 2 years. Radiation therapy alone achieves high local control in small tumors (T1-2), while large tumors (T3-4) require aggressive combined treatment, i.e., radiation and chemotherapy.     

Central nervous system dissemination in immunocompetent patients with aggressive lymphomas: incidence,risk factors and therapeutic options

Central nervous system (CNS) dissemination is a rare (4–5%) but usually fatal complication of aggressive lymphomas. Prophylaxis modalities to prevent CNS dissemination in aggressive lymphomas cannot be widely applied to every lymphoma patient since it is associated with increased risk of neurotoxicity. Therefore, identification of high‐risk patients as the best candidates to receive CNS prophylaxis constitutes a major endpoint in the management of these malignancies. Various risk factors and models for CNS recurrence have been described. Parameters reflecting the extent and proliferation of the disease, like elevated serum lactate dehydrogenase levels, involvement of multiple extranodal sites, advanced stage and high age‐adjusted International Prognostic Index (IPI) score, as well as the involvement of specific anatomic sites, like testes, orbit, paranasal sinuses, have been identified and confirmed as important to predict CNS dissemination. Management of this complication in aggressive lymphomas with conventional‐dose chemotherapy is associated with disappointing results, while some preliminary but encouraging experiences suggest a potential role of high‐dose chemotherapy and stem cell transplantation. The analysis of recent clinical studies could lead to advancement in the prognosis of aggressive lymphomas, but several questions regarding the optimum chemotherapy combination, the best conditioning regimen and the role of radiation therapy and intrathecal chemotherapy remain still unanswered. The purposes of the present review are to critically analyse current data on the risk of CNS dissemination in aggressive lymphomas, the clinical presentation of secondary CNS lymphomas and the efficacy of CNS prophylaxis as well as to discuss the available therapeutic options for this devastating event. Copyright © 2009 John Wiley & Sons, Ltd.     

Leukemic and lymphomatous meningitis: incidence,prognosis and treatment

Summary Neoplastic meningitis (NM) is a common problem in neuro-oncology occurring in approximately 5% of all patients with cancer. Notwithstanding frequent focal signs and symptoms in NM, NM is a disease affecting the entire neuraxis and therefore staging and treatment need encompass all cerebrospinal fluid (CSF) compartments. Central nervous system (CNS) staging of NM includes contrast enhanced cranial computerized tomography (CE-CT) or magnetic resonance imaging (MR-Gd), contrast enhanced spine magnetic resonance imaging (MR-S) or computerized tomographic myelography (CT-M) and radionuclide CSF flow study (FS). Treatment of NM involves involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy may benefit patients with NM and may obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (i.e. methotrexate, cytosine arabinoside and thio-TEPA) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of NM is palliative with an expected median patient survival of 4 to 6 months, it often affords stabilization and protection from further neurologic deterioration in patients with NM. In patients with leukemia or lymphoma, prophylaxis of the CNS is used (utilizing a combination of high-dose systemic chemotherapy and intra-CSF chemotherapy) for patients at high risk as defined by specific tumor-related laboratory markers. Using such a risk-stratified approach, the late occurrence of CNS relapse has decreased dramatically attesting to the value of CNS prophylaxis.     

Follicular large cell lymphoma: analysis and prognostic factors in 62 patients

Sixty-two patients with follicular large cell lymphoma were treated between 1973 and 1981. The overall median survival was 78 months with a five-year survival of 62%. The complete remission rate was 76%, with a median relapse-free interval of 72 months for responders. Complete remission produced a significantly longer survival than partial response and failure. Patients who tolerated therapy with an intensive doxorubicin-containing regimen had a significantly longer relapse-free interval and survival. Patients with stage I-II disease treated with radiation therapy alone had a higher relapse rate than those treated with radiation and combination chemotherapy. The addition of radiation therapy to combination chemotherapy in stage III-IV disease decreased the incidence of relapse at irradiated sites, but did not translate into improved survival. Pretreatment prognostic factors associated with poor response were thrombocytosis and stage III-IV disease; those associated with shortened survival were thrombocytosis, elevated lactic dehydrogenase level, stage III-IV disease, and bulky abdominal disease. Follicular large cell lymphoma is an aggressive lymphoma. Treatment should be curative in intent, and should include intensive combination chemotherapy even in stage I-II disease. Knowledge of important prognostic factors can be useful for analysis of future trials and planning therapeutic strategies.