Intensive chemotherapy for peripheral T-cell lymphomas.

Forty-two patients with previously untreated peripheral T-cell lymphomas (PTCL) were treated with an intensive chemotherapy protocol. Either the BACOP or the m-BACOD regimen was used for induction. Patients achieving complete clinical remission after three courses were given intensive consolidation and maintenance chemotherapy similar to the L10/L17M protocol designed by the Memorial Sloan-Kettering Group for acute lymphoblastic leukemia and lymphoblastic lymphoma. There were 27 (64 per cent) males and 15 (36 per cent) females. The median age was 54 years (mean 53, range 15 to 68). Seven of them (17 per cent) had stage I disease, four (10 per cent) stage II, seven (17 per cent) stage III and 24 (57 per cent) stage IV. Eighteen patients (43 per cent) had B symptoms and four (10 per cent) had bulky disease. According to the Working Formulation, the histology was diffuse mixed in 16 patients (38 per cent), diffuse large cell in 18 (43 per cent), diffuse immunoblastic in four (10 per cent) and unclassifiable in four (10 per cent). According to a modified Japanese Lymphoma Study Group's classification, the histology in 24 patients (57 per cent) was the pleomorphic type, in 13 (31 per cent) immunoblastic-lymphadenopathy-like (IBL-like), and in five (12 per cent) unclassifiable. The overall complete remission rate was 67 per cent. Twenty-five per cent of the complete responders relapsed and the DFS of the CR patients was 62 per cent at three years. The overall survival of all patients at three years was 52 per cent. Patients with stage I, II and III disease had significantly better CR rate (100 per cent versus 42 per cent, p = 0.001) and overall survival (82 per cent versus 35 per cent at three years, p = 0.01) than those with stage IV disease but the relapse rate and DFS of CR patients were similar. This study shows that the prognosis of patients with PTCL can be improved by intensive therapy.     

Management of stage I-II diffuse aggressive non-Hodgkin's lymphoma of the Waldeyer's ring: combined modality therapy versus radiotherapy alone

Twenty five patients with stage I and II diffuse aggressive non-Hodgkin's lymphoma of the Waldeyer's ring were reviewed. There were 19 patients with diffuse histiocytic, 4 diffuse lymphocytic poorly differentiated and 2 diffuse mixed lymphoma. Their median age was 51 years. There were 12 males and 13 females. Eight patients had stage I, and 17 had stage II disease. There was a significantly higher incidence of involvement of the left side of the Waldeyer's ring compared to the right (p = 0.0251). Fifteen patients received radiotherapy alone, and ten had radiotherapy and chemotherapy. The median durations of follow-up were 42 (range 8-162) and 44 (range 8-97) months respectively. All patients had complete remission but 9 patients (36 per cent) subsequently had relapse of their lymphomas. Stomach was the commonest site of relapse (44 per cent). The disease free survival and overall survival at 5 years were 59 per cent and 57 per cent respectively. Higher relapse rate was observed in the radiotherapy alone group (60 per cent) as compared to the combined modality therapy group (0 per cent). Patients who received combined modality therapy had significantly superior 5 years disease free survival (100 per cent versus 32 per cent, p less than 0.01) and overall survival (81 per cent versus 40 per cent, p less than 0.05). After radiotherapy alone, patients with stage II disease appeared to have a high relapse rate than those with stage I disease (70 per cent versus 40 per cent) but the difference did not reach statistical significance due to small sample sizes. The histological subtypes did not appear to affect their prognosis. All patients with stage I and II diffuse aggressive non-Hodgkin's lymphoma of the Waldeyer's ring should have gastrointestinal barium studies at initial staging, and a prospective randomised study on these patients comparing radiotherapy alone and combined modality therapy should be performed.     

Factors affecting remission and survival in patients with advanced Hodgkin's disease treated with MVPP

One hundred and fourteen patients with clinical or pathological stages IIIB and IV Hodgkin's disease have been treated with MVPP chemotherapy followed by radiotherapy to sites of previously bulky disease. The minimum follow-up is 2 years with a median of 5 years. The overall remission rate was 92 per cent with 74 per cent achieving CR. A discriminant analysis showed that the presence of bulky disease was the only independent factor that predicted a lower chance of CR (66 per cent vs 82 per cent, P = 0.045). The 5-year survival was 70 per cent overall and 85 per cent for CR patients. A Cox multivariate analysis demonstrated that stage III disease, age less than 36 years and female sex were all variables which independently predicted a more favourable prognosis in terms of overall survival. However, a similar analysis for survival of CR patients showed that age less than 36 years and the absence of bulky disease were the only two factors to independently predict a more favourable outcome. Of 14 patients who did not receive the chemotherapy according to protocol 5 have relapsed compared to 7 of 70 who did. A Cox analysis confirmed that this variable was the only one of significant prognostic import in predicting relapse-free survival. Using the Cox analyses we have been able to devise a scoring system which accurately predicts the outcome for these patients. This model may be useful in determining which patients have a worse prognosis following treatment with MVPP thus allowing more intensive therapy to be given to such patients while minimising treatment for those with favourable features.     

Influence of surgical resection before and after chemotherapy on survival in small cell lung cancer

We attempted to define the role of surgery in the treatment of small cell lung cancer (SCLC). Of 81 patients with clinically localized SCLC, 36 underwent surgical resection: 19 underwent initial resection with postoperative chemotherapy, while the remaining 17 were treated initially with chemotherapy, then resection. The remaining 45 patients were treated with a combination of chemotherapy and radiotherapy. The 5-year survival for the 36 surgical patients was 38%; median survival time (MST) was 33 months. Nineteen patients treated with postoperative chemotherapy showed a 42% 5-year survival, while 17 patients treated with preoperative chemotherapy showed a 33% 5-year survival. This difference was not significant. However, stage III survival tended to be better in patients with preoperative chemotherapy (MST, 29 months) than in those who had had postoperative chemotherapy only (MST, 17 months). Although survival of the 45 nonsurgical patients was poor, stage I and II patients, or those with complete remission showed a 25% 5-year survival with an MST of 33 months, and a 21% 5-year survival with an MST of 25 months, respectively. We thus concluded that initial resection combined with postoperative chemotherapy is beneficial for patients with stage I, and probably stage II disease. For resectable stage III, particularly in patients with N2 disease, adjuvant resection after chemotherapy may be a favorable choice in the management of SCLC. For advanced stage III, complete remission by chemotherapy should be attempted in combination with radiotherapy.     

Follicular non-Hodgkin's lymphoma in Hong Kong Chinese: a retrospective analysis

Follicular lymphoma is relatively rare in Hong Kong Chinese. Fifty-two patients with follicular lymphoma were reviewed. The histology was nodular lymphocytic poorly differentiated (NLPD) in 75 per cent, nodular mixed (NM) in 21 per cent and nodular histiocytic (NH) in 4 per cent. Our patients appeared to have a higher proportion of NLPD and a lower proportion of NM lymphoma than the western series. Fifty patients were analysed excluding the two patients with NH lymphoma. They had a median age of 50 and a male to female ratio of 0.92. Seventy-two per cent of them presented with asymptomatic lymph node enlargement. Twenty per cent had B symptoms and 32 per cent bulky tumour. Twelve per cent had stage I disease, 2 per cent stage II, 30 per cent stage III and 56 per cent stage IV. A high incidence of bone marrow involvement (48 per cent of all patients) was found. All seven stage I-II patients responded to involved-field radiotherapy alone and none of them has relapsed. The 43 stage III-IV patients were treated with chemotherapy without deferral and a majority of them received CVP (51.1 per cent) or chlorambucil alone (34.9 per cent). The complete response rate of stage III-IV patients was 81 per cent and 26 per cent of the complete responders relapsed. The 5-years disease-free survival (DFS) and overall survival of all patients (stage III and IV) were 50 per cent and 65 per cent respectively. The DFS curve showed a pattern of continuous relapses. Stage III patients appeared to have a better complete response rate, a lower relapse rate and superior disease-free survival than stage IV patients but the differences did not reach statistical significance. However, the overall survival of stage III patients was significantly better than stage IV patients (p less than 0.02). Other factors including sex, age, presence of bulky tumour, B symptoms, histologic subtypes and the chemotherapeutic regimes did not significantly affect their prognosis.     

Prognostic factors in localized aggressive non-Hodgkin's lymphoma

To identify the prognostic factors that specifically predict survival rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL), a retrospective study including 118 patients with clinical stage I and II NHL treated at the Institute of oncology, Istanbul University between 1989 and 1998 was conducted. Patients were treated either with radiotherapy alone, radiotherapy and adjuvant chemotherapy, or chemotherapy (with or without adjuvant radiotherapy). The 5-year disease-free survival (DFS) and overall survival rates were calculated, and univariate and multivariate analyses were performed to identify the significance of various prognostic factors such as gender, age, performance status, stage (I versus II), B symptoms, extranodal involvement, gastrointestinal tract disease, erythrocyte sedimentation rate, bulky disease, histologic grade, serum lactate dehydrogenase level, serum beta2-microglobulin level, serum albumin level, treatment regimen, remission status, and the International Prognostic Index risk groups, which may have an influence on the outcome of patients with NHL. The overall 5-year survival rate was 52% with a median follow-up of 30 months. The complete response rate was 68%, and the 5-year DFS of complete responders was 70%. Cox multivariate regression analysis showed that incomplete response, low serum albumin, bulky disease (>10 cm), and high grade histology were the pretreatment factors associated with shorter survival. When remission status was included in the model, the attainment of a complete response was the major determinant of long-term survival; however, low albumin level was still a significant adverse predictor for survival in multivariate analysis. These factors need to be evaluated for analyzing the outcome of treatment and to identify better therapeutic strategies.     

Hodgkin's disease in adults in Saudi Arabia. Clinical features, prognostic factors and an analysis of therapy. Outcome of combination chemotherapy only, for both localized and advanced disease.

Fifty evaluable, previously untreated, adult patients with clinically staged (CS) early and advanced Hodgkin's disease were treated with chemotherapy alone, using various regimens. Their mean age was 31.9 years. Fifteen patients (30%) had CS I or II and 35 (70%) had CS III or IV. Eighty-eight per cent of patients had one or more of the B symptoms and 64% had an unfavorable histology. Complete remission (CR) was achieved in 43 out of 50 patients (86% with 95% confidence interval of 76% to 96%), partial remission in 3 (6%) and treatment failure in 4. Adjusted analysis, using all possible subset regression, showed that unfavorable histology, bulky disease and receiving a total dose-intensity (TDI) less than or equal to 0.80 were negatively associated with the likelihood of achieving CR. At a median follow-up of 36 months (range, 6-90), 84% of patients were alive and 82% were disease-free. The overall median survival has not been reached, but the projected 5-year survival probability was 79%. Time-to-relapse was also estimated for those who achieved initial CR. The estimated 5-year relapse-free survival was 87%. The Cox proportional hazards model predicted that unfavorable histology, bulky disease and TDI less than or equal to 0.80 had an independent, adverse influence on survival. We conclude that the results of chemotherapy alone are encouraging and the rationale is practical and acceptable in those countries where the availability of radiotherapy units is limited.     

Prognostic Factors in Stage I and II Non-Hodgkin's Lymphoma of Waldeyer's Ring

Sixty-nine stage I and II patients treated for non-Hodg-kin's lymphoma of Waldeyer's ring were retrospectively analysed. Diffuse histiocytic lymphoma (Rappaport's classification) was the most common histology (67%). Staging without laparotomy revealed 31 patients in stage I and 38 in stage II. Sixty-five patients received radiation therapy against involved or extended fields. In 43 patients adjuvant chemotherapy with single or multiple agents was given and 4 patients received only chemotherapy. A relapse occurred in 34 (49%) patients. The 5-year relapse-free survival was 67 per cent and 36 per cent in stage I and stage II, respectively. Radiation doses of 50 Gy gave no recurrence within treated volumes. However, since relapse below the clavicles and especially below the diaphragm was common, the radiation doses did not seem important for reduction of the overall failure rate. In stage II, patients with a single neck node less than 5 cm in diameter seemed to have a better prognosis than patients with large or multiple neck nodes. In this non-randomized study adjuvant chemotherapy seemed to reduce the risk of relapse, especially in stage II patients.     

Follicular lymphoma: prognostic factors for response and survival

One hundred forty-eight patients with newly diagnosed follicular lymphoma were treated over a 12-year period. Twenty-two patients received radiotherapy for stage I and II disease, followed by adjuvant chemotherapy in 14 patients. One hundred thirteen were treated at presentation with short courses of chemotherapy, most often with single-agent chlorambucil for bulky stage II and stages III and IV disease. Thirteen patients were managed expectantly until there was evidence of disease progression. The median survival was 9 years. Patients treated with radiotherapy for stage I and II disease had an 83% relapse-free survival, but those with bulky stage II or stages III and IV disease treated with chemotherapy pursued a remitting and relapsing course with a 70% response rate at initial and subsequent retreatments, but a median duration of remission of 4 years in stage III and 1 year in stage IV disease (P = .041). Patients were observed in relapse and retreatment was administered as appropriate, once every 33 months on average. Poor prognosis patients could be identified by a combination of the presentation characteristics: B symptoms, hepatosplenomegaly, anemia, and abnormal liver function. These factors predicted a poor response to treatment and correlated with a short survival. Histologic subgroups were not associated with differences in survival, but transformation to a diffuse high-grade lymphoma was observed in 23 of the 72 patients (32%) at risk, with a median follow-up of 6 years and 6 months, and was associated with a very poor prognosis. The present treatment strategy has proved successful for most patients with localized disease and those older patients with indolent small volume disseminated follicular lymphoma. New approaches are being investigated for the younger poor prognosis patients.     

Prognostic factors for primary gastrointestinal lymphoma

The gastrointestinal tract is a common primary extranodal site for non-Hodgkin's lymphoma. There is however no uniform consensus on its pathological classification, clinical staging system and management. This paper reports the experience in the management of 425 Chinese patients with primary gastrointestinal lymphoma in Hong Kong from January 1975 to June 1993. There were 230 (54 per cent) males and 195 (46 per cent) females. Their median age was 53 years. The primary sites were: the esophagus in three (1 per cent), stomach in 238 (56 per cent), small intestine in 131 (31 per cent) and large intestine in 53 (12 per cent). According to the Working Formulation, there were 20 (4.7 per cent) small lymphocytic, 10 (2.4 per cent) follicular small cleaved cell, 15 (3.5 per cent) follicular mixed, five (1.2 per cent) follicular large cell, 40 (9.4 per cent) diffuse small cleaved cell, 50 (12 per cent) diffuse mixed, 181 (43 per cent) diffuse large cell, 30 (7.1 per cent) immunoblastic, five (1.2 per cent) lymphoblastic, 10 (2.4 per cent) diffuse small non-cleaved cell and 50 (14 per cent) unclassifiable lymphoma. Immunophenotyping was performed in 199 (47 per cent) patients: 90 per cent B-cell, 7 per cent T-cell and 3 per cent uncertain. According to a Manchester system, 81 (19 per cent) patients had stage I disease, 44 (10 per cent) stage II, 85 (20 per cent) stage III and 215 (51 per cent) stage IV. B symptoms were present in 275 (65 per cent) patients and bulky disease in 104 (25 per cent). Surgery followed by chemotherapy was the mainstaly of treatment. Of the 408 patients treated, 63 per cent had a complete remission with relapse rate of 42 per cent. For those with complete remission, 47 per cent were free from disease at 5 years. The overall median survival of all patients was 45 per cent at 5 years. Multivariate analysis revealed that significant independent prognostic factors predicting better survival were young age of <60 years, low grade histology, stage I and II disease and absence of bulky tumour. For gastric lymphoma, aggressive surgery did not significantly improve their outcome. Chemotherapy appears to play an important role in the management of gastrointestinal lymphoma. Better classification of the primary gastrointestinal lymphoma and more refined stratification of the patients according to the prognostic variables my allow individualization of treatment. Prospective randomized studies are essential to define the relative roles of surgery, chemotherapy and radiotherapy.     

Bulky mediastinal Hodgkin's disease management and prognosis

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

Risk-adapted, combined-modality therapy with VAMP/COP and response-based, involved-field radiation for unfavorable pediatric Hodgkin's disease.

PURPOSE: To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease. PATIENTS AND METHODS: From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or "B" symptoms and all stage III and IV. RESULTS: Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% +/- 2.5% and 75.6% +/- 4.1%, respectively. CONCLUSION: Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease.     

Stages I and II non-Hodgkin's lymphomas of Waldeyer's ring and the neck

In a previous communication we reported our results for patients with localized extranodal presentations of non-Hodgkin's lymphomas of the head and neck who were admitted between 1961-1969. This review describes our larger experience from 1947-1982 in treating 137 Stages I and II Waldeyer's ring patients whose slides were available for reclassification according to the modified Rappaport System. All of these patients were treated definitively as follows: radiotherapy only, 113 patients; radiotherapy and combination chemotherapy, 17 patients; chemotherapy only, seven patients. The overall 5-year survival was 50%. Significant differences were determined for specific subgroups. For patients staged after lymphangiography, the 5-year survival was 67% as compared with 32% for non-lymphangiogram staged patients (p = 0.002). Stage (Ann Arbor) also influenced results. The 5-year survival figure for Stage I was 70% as compared with 42% for Stage II (p = 0.002). The combination of extent of disease in Waldeyer's ring and the status of the neck had a major impact on survival. When the disease was staged according to the TNMAJCC System, the 5-year survivals were: 75% for T1-T2-TX N0; 53% for T1-T2-TX N+; 54% for T3-T4 N0; and 36% for T3-T4 N+. Also, results for tonsil (52%) and base of tongue (66%) disease were better than for disease involving the nasopharynx (39%) or multiple sites (25%). Treatment also influenced survivals and disease-free survivals. The best results were obtained in patients who were treated with radiotherapy and combination chemotherapy. The 5-year survival and disease-free survival figures were 78% and 69%, respectively.     

Survival after relapse in children and adolescents with rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study Group.

BACKGROUND: Despite advances in therapy, nearly 30% of children with rhabdomyosarcoma experience progressive or relapsed disease, which is often fatal. PATIENTS AND METHODS: To facilitate the development of a retrieval therapy protocol, we studied potential risk factors that were predictive of survival after first relapse in 605 children who were enrolled onto three consecutive Intergroup Rhabdomyosarcoma Study Group protocols. RESULTS: The median survival time from first recurrence was 0.8 years; the estimated percentage of patients who survived 5 years from first recurrence was 17% +/- 2% (mean +/- SD). Univariate analysis showed that tumor histology was an important predictor of 5-year survival (P <.001): the 5-year survival rate was 64% for patients with botryoid tumors (n = 19), 26% for patients with embryonal tumors (n = 313), and 5% for patients with alveolar or undifferentiated sarcoma (n = 273). Further analysis identified prognostic factors within histologic subtypes (P <.001). For patients with embryonal tumors, the estimated 5-year survival rate was 52% for patients who initially presented with stage 1 or group I disease, 20% for those with stage 2/3 or group II/III disease, and 12% for those with group IV disease. For patients with stage 1/group I disease, estimated 5-year survival rates were higher for patients with local (72%) or regional (50%) recurrence than for those with distant (30%) recurrence. Among patients with alveolar or undifferentiated sarcoma, only the disease group predicted outcome: the 5-year survival estimate was 40% for group I versus 3% for groups II through IV. We identified a "favorable risk" group (approximately 20% of patients) whose 5-year estimated survival rate was near 50%; for all other patients, the estimated survival was near 10%. CONCLUSION: This analysis demonstrates that the probability of 5-year survival after relapse for rhabdomyosarcoma is dependent on several factors at the time of initial diagnosis, including histologic subtype, disease group, and stage. These findings will form the basis of a multi-institutional risk-adapted relapse protocol for childhood rhabdomyosarcoma.     

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

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

Management of localized non-Hodgkin's lymphoma: the experience at St. Bartholomew's Hospital 1972-1985

A retrospective study of 202 patients with clinical stage I and II non-Hodgkin's lymphoma managed at St. Bartholomew's Hospital between 1972 and 1985 was conducted. Patients were treated either with radiotherapy alone, radiotherapy and adjuvant chemotherapy, or chemotherapy (with or without adjuvant radiotherapy). At the onset of the study it was intended that all patients with localized NHL should be treated with involved field radiotherapy and adjuvant 'CVP'. As it became apparent that this was inadequate for some patients and too toxic for others a flexible approach was later adopted. Treatment selection depended on age, volume, distribution of disease and histological subtype. The actuarial 5 year overall survival for the whole group was 70 per cent. Death from lymphoma after 5 years was very rare. Increasing age and high grade histology were highly significant adverse prognostic factors by multivariate analysis. The results for patients with high grade and low grade histology were therefore analysed separately, as was the outcome for patients presenting with either gastrointestinal or skin lymphomas. During the latter part of the study period intensive chemotherapy was given as the initial treatment to patients with high grade histology and bulky, or stage II disease. Twenty out of 24 patients so treated achieved complete remission and only one has relapsed to date. These results are encouraging and probably explain the absence of a difference in prognosis between patients with stage I and IE disease and those with stage II and IIE disease observed over the whole period of the study. Remission was achieved in the overwhelming majority of patients with low grade histology for whom radiotherapy was selected as primary therapy. Duration of remission was better in patients who received adjuvant chemotherapy than in those treated with radiation alone, but no difference in overall survival was observed between these groups. Neither stage nor the presence of a follicular histological pattern correlated with prolonged survival in patients with low grade histology.     

A review of californium-252 neutron brachytherapy for cervical cancer

Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron-emitting radioactive isotope, californium-252 (Cf-252), for the treatment of cervical cancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced (Stages III and IV) cervical cancer patients using different doses and schedules; they were extended to include unfavorable presentations of Stages I and II because of favorable results in the initial trials. The authors began to treat patients with Stage IB bulky or barrel-shaped tumors and the majority were treated with both radiation and hysterectomy. Actuarial survival was determined for Stage IB disease and was 87% at 5 years and 82% at 10 years. For those tested with preoperative radiation it was 92% at 5 and 87% at 10 years. For Stage II, it was 62% 5 years and 61% at 10. Survival 5 years after combined radiation and surgical therapy for Stage II disease was 68%. For Stage III, it was 33% at 5 years and 25% at 10. However, 5-year survival using the early neutron implant was 46% versus approximately 19% for delayed Cf-252 or cesium 137. Different schedules and sequences of neutrons and photons greatly altered outcome. Neutron treatment before external photon therapy was better for all stages of disease. Only about 5% of all patients developed complications after neutron therapy. No hematologic or mesenchymal second tumors were observed. Neutron brachytherapy was found to be very effective for producing rapid response and greatly improved local control of bulky, barrel, or advanced cervical cancers. The clinical trial identified and evolved schedules, doses, doses per session, and developed methods different from standard photon therapy but highly effective for local control and cure of cervical cancers of all stages. Clinical and radiobiologic understanding for the use of neutron therapy was greatly advanced by this trial. Future trials will focus on patients with advanced disease and will require evaluation of adjuvant chemotherapy studies and neutron-enhancing chemicals.     

Nodular histiocytic lymphoma, emphasizing results of stage I disease treated by radiotherapy. A report of the Japan Lymphoma Radiation Therapy Study Group (JLRTG)

The records of 49 patients with nodular histiocytic lymphomas (NH) who were treated from 1972 to 1985 in hospitals belonging to the JLRTG were retrospectively reviewed. The actuarial survival rate and relapse-free survival rate of all patients after 5 years were 55.0 and 51.3%, respectively. Twenty-one patients with stage I disease had a significantly better survival rate than did 12 patients with stage II disease (P less than 0.01). Without combination chemotherapy, all 15 patients with stage I NH treated by radiation therapy were in complete remission, and 14 of them remained alive and well. Among these 15 patients, no difference in relapse was observed between patients who received involved field irradiation (1 of 6) and those who received extended field irradiation (2 of 9). Patients with stage II or more NH should be treated with intensive chemotherapy and radiotherapy, as are patients with diffuse histiocytic lymphoma (DH). However, involved field radiotherapy with careful follow-up observation may be the treatment of choice for patients with stage I NH, provided their tumors are not bulky.     

A Therapeutic Approach to Early Vocal Cord Carcinoma

One hundred and twenty patients with early glottic carcinoma received radiation therapy at the University of Maryland Hospital from 1959 to 1977. The radiation dose ranged from 55 Gy in 4 weeks for small Tla lesions to 65 Gy in 6¹/₂ weeks for T2 lesions. The local control rates by irradiation alone for stages Tla, Tlb, and T2 were 92, 91 and 88 per cent, respectively, while 5-year determinate disease-free survival rates were 96 per cent for stage I disease and 88 per cent for stage II disease. Most of the local failures were salvaged by surgery, with a low complication rate. Regional metastases were uncommon, and occurred in 7 per cent in stage I and in 6 per cent in stage II disease. Factors increasing the risk of failures appeared to be bulky tumor, anterior commissure involvement and subglottic extension.     

Chemotherapy as definitive treatment of stage I-II large cell and diffuse mixed lymphomas

Combination chemotherapy with adriamycin-containing regimens is effective in the management of advanced lymphomas. In view of this, we treated 43 patients with clinical stage I-II large cell or diffuse mixed lymphoma with chemotherapy. Routine staging laparotomies were not done and radiotherapy was not used in these patients. The CR rate for the combined stage I-II presentations is 90%. Of 11 patients with stage I presentations, only one has relapsed (at 64 months), and he expired 11 months after the recurrence. Of the 28 patients with stage II presentations who achieved a CR, seven have relapsed but three of these have achieved a second CR and remain in remission. Late relapses were common in this group of stage I-II presentations. Four of eight relapses occurring in patients who achieved disease-free status took place greater than 24 months after initiation of therapy. Chemotherapy alone appears to be adequate for treatment of stage I large cell lymphoma, although larger numbers of patients might be required to definitely make this conclusion. Close to 2/3 of patients with stage II presentations appear to have been cured with the use of chemotherapy alone. The failures occurred mostly in those with bulky disease. It is possible that radiotherapy given after chemotherapy could consolidate these bulky areas of disease and thus prevent local relapses.