End-of-treatment but not interim PET scan predicts outcome in nonbulky limited-stage Hodgkin's lymphoma.

BACKGROUND: Early interim positron emission tomography (PET) scans appear powerfully predictive of outcome in Hodgkin's lymphoma (HL), particularly in advanced-stage disease where it has been predominantly studied. The prognostic value of interim PET in limited-stage patients with nonbulky disease has not been well established. PATIENTS AND METHODS: Ninety-six patients with nonbulky limited-stage HL were identified who had interim and end-of-treatment PET scans. Response rate, overall survival (OS), and progression-free survival (PFS) were calculated. RESULTS: Four-year PFS and OS for the entire cohort were 88% and 97%, respectively. Interim PET did not predict outcome, with PFS in positive and negative patients 87% versus 91% (P=0.57), respectively. End-of-treatment PET result was predictive of outcome, with PFS of 94% in end PET-negative patients versus 54% in end PET-positive patients (P<0.0001). Four-year OS was 100% in end PET-negative patients and 84% in end PET-positive patients (P<0.0001). CONCLUSIONS: Interim PET scans were not predictive of outcome, compared with scans carried out at completion of therapy. End-of-treatment PET was highly predictive of PFS and OS, regardless of interim PET result. In this low-risk patient population, even patients with interim positive PET scans show a favorable prognosis.

Evidence for genetic restriction in the suppression of erythropoiesis by a unique subset of T lymphocytes in man.

The suppression of erythropoiesis by lymphocytes from patients with a T cell lymphoproliferative syndrome and pure erythrocyte aplasia has been previously demonstrated. To study the nature of the suppressor cell and possible genetic restriction of this suppression, we investigated a patient with severe anemia, splenomegaly, lymphocytosis, and erythroid aplasia. A 3-mo course of low-dose daily oral cyclophosphamide achieved a complete remission for over 12 mo. The surface phenotype of his lymphocytes was analyzed by means of antibodies to lineage, differentiation, and activation-specific surface antigens. The cells expressed mature T cell antigens T3, T8, and T11, while lacking T1. Immature T cell, B cell, and the monocyte-specific antigen Mo2 were absent, while Mo1, a monocyte-associated antigen not normally expressed on T cells, was present. T10 and Ia expressed as activation antigens were also present. The cells, cryopreserved at diagnosis, were thawed and co-cultured in plasma clot with patient remission marrow samples at T cell/bone marrow ratios of 1:1 and 2:1. There was nearly 90% suppression of erythroid colony-forming unit expression and 60% suppression of erythroid burst-forming unit expression at 2:1 T cell to bone marrow ratios and somewhat less suppression at 1:1. Granulocyte/macrophage progenitor expression was unaffected. Erythroid progenitor differentiation in the marrows of two HLA identical siblings was similarly suppressed. The cells were co-cultured with the marrows of nine nonrelated donors to investigate the potential genetic restriction of this suppression. Colony suppression equal to that observed in the marrow of the patient and his siblings was found in studies of two partially HLA identical individuals. No suppression was detected in marrow co-cultures of two entirely HLA dissimilar individuals. These results show that suppression of erythropoiesis by a unique subset of T8, Mo1, Ia-positive lymphocytes isolated from a patient with lymphocytosis and erythrocyte aplasia is genetically restricted.

Comparison of adjuvant chemotherapy with methotrexate and fluorouracil with and without cyclophosphamide in breast cancer patients with one to three positive axillary lymph nodes.

BACKGROUND: Alkylating agents administered as single agents or in combination with antimetabolites or anthracyclines delay the appearance of metastases and prolong the survival of breast cancer patients after surgery. PURPOSE: This phase III clinical trial was designed to evaluate the therapeutic efficacy and toxicity of the alkylating agent cyclophosphamide in combination with the antimetabolites methotrexate and fluorouracil adjuvant to breast cancer surgery. METHODS: This study consisted of 255 breast cancer patients (a) with one to three histologically positive axillary lymph nodes and either no detectable primary tumor or operable primary tumors 5 cm or less (T0-T2) (95% of the patients) or (b) with tumors larger than 5 cm (T3) and with negative axillary nodes. Patients were randomly allocated to receive either methotrexate (60 mg/m2) and fluorouracil (600 mg/m2) (MF) intravenously on days 1 and 8 every 28 days for eight cycles or cyclophosphamide (100 mg/m2) orally on days 1-14 plus MF (CMF) every 28 days for the same duration. Median follow-up was 7.8 years, and maximum follow-up was 13 years. RESULTS: There were no statistically significant differences in time to treatment failure or overall survival for patients treated with MF or CMF. At 8 years after completion of treatment, time to treatment failure was 55% (95% confidence interval [CI] = 50%-60%) and 59% (95% CI = 54%-64%) and overall survival was 69% (95% CI = 65%-73%) and 67% (95% CI = 62%-72%) for MF- and CMF-treated patients, respectively. The hazard ratios (MF to CMF) for time to treatment failure and for survival, estimated with a proportional hazards model, were 1.02 (95% CI = 0.69-1.50) and 0.87 (95% CI = 0.56-1.34), respectively. Myelosuppression was significantly greater (P < .0001) in CMF-treated patients during cycles 1-6. Median white blood cell count nadirs were between 4.4 x 10(3)/microL and 3.5 x 10(3)/microL in patients receiving MF and between 3.0 x 10(3)/microL and 2.4 x 10(3)/microL in those receiving CMF. Dose reductions were more frequent in CMF-treated patients, which led to statistically significant differences (P < .0001) in amounts of methotrexate and fluorouracil administered. Primary cancers at other sites occurred in 14 patients (5.5%)--six treated with MF and eight treated with CMF. CONCLUSIONS: Our findings suggest that the addition of cyclophosphamide to adjuvant chemotherapy with MF offers no therapeutic advantage but results in increased myelosuppression. IMPLICATIONS: Future trials will define the possible advantages of antimetabolites in adjuvant therapy. Further information will also become available when results of the ongoing National Surgical Adjuvant Breast and Bowel Project trial comparing adjuvant MF to CMF in node-negative breast cancer patients are presented.

Structural and functional effects of adriamycin on cardiac cells in vitro.

The effects of Adriamycin (ADR) on the heart, seen clinically as transient electrocardiographic changes and cardiomyopathy, have been simulated in an in vitro cardiac cell system. Structural and functional alterations in cultured heart cells can be dissociated based upon ADR dose and length of exposure. At high ADR doses (100 to 200 micrograms/ml), cessation of beating was rapid, and structural changes consistent with the in vivo cardiomyopathic picture (vacuolization and nucleolar fragmentation) were observed. At low ADR doses (0.1 to 0.5 micrograms/ml), arrhythmias were produced in the absence of ultrastructural changes (within 48 hr); the incidence and severity of the arrhythmias were demonstrated to be dose dependent. Continued treatment of cultures at low dose levels for sustained periods of time (up to 17 days) resulted in a striking loss of muscle fiber without concomitant vacuolization and nucleolar fragmentation. An intermediate ADR dose of 10 micrograms/ml for 1 hr exposure caused vacuolization and cessation of beating, with lysis of cells within 72 hr. The parallel between the effects of ADR on in vitro cardiac cell structure and function with those seen in vivo suggests that this simple system may have value in studies directed towards the mechanism of ADR-induced cardiac toxicity and in the screening of anthracycline analogs for their potential effects on the heart.

Burnout syndrome in the practice of oncology: results of a random survey of 1,000 oncologists.

Burnout, the end result of stress, can occur in any profession. We set out to determine the extent of burnout among a representative group of American oncologists. A questionnaire with 12 specific points was designed and prepared by the authors. It was mailed to 1,000 randomly selected physician subscribers to the Journal of Clinical Oncology. Five hundred ninety-eight completed surveys (60%) were returned before the cut-off date and included in the analysis. Overall, 56% of the respondents reported experiencing burnout in their professional life. No significance was found between the incidence of burnout and specialty within oncology, year medical training ended, or practice location. Significance was found, however, between type of practice and the incidence of burnout; institution- or university-based oncologists reported a lower incidence of burnout (47%) versus all other types of practice (66% burnout rate for oncology plus internal medicine, 63% for private adult oncology only, 39% for pediatric oncologists [there were too few pediatric oncologists for this rate to be significant], and 64% for others; P = .0003). Frustration or a sense of failure was the most frequently chosen (56%) description of burnout, and insufficient personal and/or vacation time was the most frequent reason (57%) chosen to explain the existence of burnout. To alleviate burnout, the majority (69%) of respondents indicated the need for more vacation or personal time. Administering palliative or terminal care, reimbursement issues, and a heavy work load were identified as contributing factors to burnout. Given the high response to the questionnaire and a 56% incidence of burnout in the surveyed population, it is concluded that further research on this issue is required.

Chemotherapy of refractory germ cell cancer with Etoposide.

Eighteen patients with advanced germ-cell cancer (12 primary gonadal, six extragonadal) that was refractory to vinblastine (V), cisplatin (P), and bleomycin (B) were treated with Etoposide (VP-16-213) and cisplatin +/- bleomycin sulfate +/- doxorubicin hydrochloride. All patients experienced nausea, vomiting, alopecia, and myelosuppression. There were no treatment-related deaths. Five (42%) of 12 patients with primary gonadal germ-cell cancer achieved a complete remission and are presently alive with no evidence of disease. None of the six patients with extragonadal germ-cell cancer achieved a complete response. Thirteen patients died 6.2 months (median) after starting Etoposide treatment. Etoposide-containing chemotherapy is useful in patients with primary gonadal germ-cell cancer. Alternative therapies are needed for patients with extragonadal germ cell cancer.

Value of follow-up procedures in patients with large-cell lymphoma who achieve a complete remission.

Salvage therapy for relapsed large-cell lymphoma (LCL) is more effective in patients with minimal disease, suggesting that early detection of relapse might increase the chance of long-term survival. To determine whether current follow-up procedures are effective in identifying preclinical disease, we analyzed patterns of relapse in 139 LCL patients who achieved a complete remission (CR) with high/moderate-dose methotrexate with leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M/m-BACOD). The timing and results of all posttreatment follow-up tests were examined in the 36 patients who relapsed from complete remission (CR) and 46 controls who remain in CR. Despite conscientious posttreatment follow-up, only two of the 36 relapses (6%) were detected before the development of symptoms. Sixty-seven percent of patients relapsed in new disease sites (42% in new and old sites, and 25% in new sites only). Consistent with this observation, the tests most sensitive to clinical relapse were those not targeted to specific sites of disease: gallium scan (sensitivity, 90%), physical examination (80%), and lactate dehydrogenase (LDH) (65%). Of screening tests performed, only LDH was successful in detecting preclinical relapse, with a sensitivity of 42% and specificity of 85% for impending symptomatic relapse. These results indicate that conventional screening was ineffective in detecting preclinical relapse in LCL patients. We recommend prospective evaluation of a strategy that (1) screens with a frequency appropriate to a patient's risk of relapse, (2) uses sensitive test(s) not targeted to specific sites, and (3) limits aggressive screening to those high-risk patients eligible for potentially curative salvage therapy.

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

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

Autologous bone-marrow transplantation: host effects of high-dose BCNU.

Thirty-five patients with solid tumors received 44 courses of bis-chlorethylnitrosourea (BCNU) at doses ranging between 600 and 1,400 mg/m2 with cryopreserved or fresh autologous bone-marrow support. Eight patients treated at 600 mg/m2 received no bone-marrow support for their first course of BCNU. Maximum follow-up was 25 months (median, four months). Myelosuppression was severe and dose related but was less prolonged in the marrow-supported groups (p = 0.01) and was not dose limiting. Myelosuppression-related toxicity of infection and hemorrhage occurred in 21 (47%) of 44 courses of treatment. Pulmonary toxicity occurred in seven of 35 patients; abnormal liver function occurred in 18 of 30 patients greater than one month from treatment; and central nervous system symptoms that may have been drug related occurred in six of 35 patients. There was no renal or cardiac toxicity. Except for myelosuppression, toxicity was not dose related. Treatment-related deaths included four with pulmonary toxicity, two with liver toxicity, sepsis in four, and gastrointestinal tract toxicity in one patient. We conclude that the limiting side effect of high-dose BCNU (greater than or equal to 600 mg/m2) is visceral toxicity; the extent of myelosuppression is shortened by the infusion of bone marrow, whether cryopreserved or fresh; and marked tumor regression can be achieved with high-dose BCNU.

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

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

Stage IA-IIB Hodgkin's disease: staging and treatment of patients with large mediastinal adenopathy.

Ninety-two patients with clinically staged (CS) IA-IIB Hodgkin's disease (HD) with large mediastinal adenopathy (LMA) underwent three different staging and treatment approaches between April 1969 and December 1984. These approaches included: (1) staging laparotomy followed by radiation therapy (RT) alone; (2) staging laparotomy followed by combined RT and chemotherapy (CMT); or (3) clinical staging followed by CMT. Patients treated with CMT were more likely to have "B" symptoms, extension into extranodal sites, or stage III disease. Patients treated with RT alone had a significantly higher risk of relapse as compared to patients receiving CMT. No overall survival differences were seen between the three groups of patients. For patients treated with CMT without RT to the spleen or abdominal nodes, the risk of relapse in the abdomen was low (4%). These data suggest that for those CS I-II HD patients with LMA who are treated with CMT, the role for staging laparotomy and abdominal irradiation is limited. RT alone remains an option for some patients with LMA, but careful assessment of the anatomic extent of thoracic disease as well as staging laparotomy is essential if such treatment is recommended.

Etoposide, vinblastine, and doxorubicin: an active regimen for the treatment of Hodgkin's disease in relapse following MOPP. Cancer and Leukemia Group B.

PURPOSE: To evaluate the activity and toxicity of combined etoposide, vinblastine, and doxorubicin (EVA) in advanced Hodgkin's disease (HD) in relapse from or refractory to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). PATIENTS AND METHODS: Eligible patients were more than 15 years of age and had received only one prior course of MOPP and were in relapse with measurable disease. The EVA regimen (etoposide 100 mg/m2 intravenously [IV] on days 1, 2, and 3; vinblastine 6 mg/m2 IV on day 1; and doxorubicin 50 mg/m2 IV on day 1) was administered every 28 days for a minimum of four and a maximum of six cycles. Patients were restaged at 3 and 6 months. RESULTS: Forty-five eligible patients were treated, with an overall response rate of 73%. There were 40% complete responses (CRs) and 33% partial responses (PRs). The median follow-up time in 42 months. The median time to treatment failure (TTF) is 10 months, with 31% continuing progression-free. Eighteen patients achieved a second CR, with only seven recurrences in that group. Failure-free survival and overall survival were significantly better in patients whose first MOPP-induced remission was longer than 12 months and who were free of B symptoms at relapse. Toxicity was primarily myelosuppression, which resulted in two toxic deaths. Pulmonary toxicity was not observed. CONCLUSION: EVA is an effective second-line regimen for the treatment of HD in relapse following MOPP chemotherapy.

High-dose CHOP as initial therapy for patients with poor-prognosis aggressive non-Hodgkin's lymphoma: a dose-finding pilot study.

PURPOSE: To purpose of this study was to develop a more effective approach to the treatment of patients with poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty newly diagnosed patients with bulky (> or = 10 cm) advanced-stage aggressive NHL were enrolled onto a pilot study. The study was designed to determine the maximum-tolerated dosages (MTD) of cyclophosphamide and doxorubicin that could be used in a high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen with granulocyte colony-stimulating factor (G-CSF) support and to assess preliminarily the efficacy of the regimen. RESULTS: In the initial dose-finding portion of the study, cumulative thrombocytopenia was the dose-limiting toxicity. At the MTD, the regimen included four 21-day cycles of cyclophosphamide 4 gm/m2, doxorubicin 70 mg/m2, vincristine 2 mg, and prednisone 100 mg for 5 days with mesna and G-CSF support. At the MTD, 65% of treatment cycles were complicated by febrile neutropenia, 84% of patients received at least one platelet transfusion for platelet counts less than 20,000/microL, and there was one treatment-related death. Nineteen of 22 (86%; 90% confidence interval [CI], 68 to 96) patients treated at the MTD achieved an initial complete response (CR), and 79% (90% CI, 58 to 92) of the complete responders and 69% of all patients remain progression-free with 20 months median follow-up. CONCLUSION: The high-dose CHOP regimen may be an effective alternative for patients with poor-prognosis aggressive NHL.

Early restaging gallium scans predict outcome in poor-prognosis patients with aggressive non-Hodgkin's lymphoma treated with high-dose CHOP chemotherapy.

PURPOSE: This prospective study assessed the predictive value of early restaging gallium (Ga) and computed tomographic (CT) scans in poor-prognosis patients with aggressive non-Hodgkin's lymphoma (NHL) who were treated with high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. PATIENTS AND METHODS: Thirty newly diagnosed patients with bulky (> or = 10 cm) advanced-stage aggressive NHL were treated with a four-cycle high-dose CHOP regimen (22 patients at maximum-tolerated dose [MTD]: cyclophosphamide 4 g/m2, doxorubicin 70 mg/m2, vincristine 2 mg, and prednisone 100 mg orally for 5 days). All patients had chest/abdominal/pelvic CT scans and 10-mCi Ga scans at baseline and following two and four cycles of therapy. Scans were reviewed in a blinded manner for CT-documented rates of response and sizes of residual masses and Ga avidity of residual masses. The results of early (post-cycle 2) and final (post-cycle 4) restaging were subsequently associated with clinical outcome. RESULTS: CT-documented rates of response and residual mass sizes were indistinguishable in complete responders who remained continuously disease-free (CR-Cont), complete responders who subsequently relapsed (CR-Rel), and partial responders who then progressed (PR/Prog). In marked contrast, early restaging (post-cycle 2) Ga scans accurately delineated these three categories of patients: CR-Cont 90% Ga-negative (18 of 20 patients) versus CR-Rel 25% Ga-negative (one of four patients) versus PR/Prog 0% Ga-negative (zero of six patients) (P = .000014). At a median follow-up duration of 31 months (range, 21 to 46), 94% of patients who had negative early restaging Ga scans remain free from progression (FFP), whereas only 18% of patients who had positive early restaging Ga scans remain FFP (P = .000007). Early restaging Ga scans were more predictive for FFP than final restaging Ga scans because patients who required four full cycles of therapy to become Ga-negative were more likely to develop recurrent disease. CONCLUSION: Early restaging Ga scans delineate patients who are likely to have prolonged disease-free survival from those who fail to respond to intensive induction therapy. Patients whose tumors remain Ga-positive midway through high-dose CHOP therapy have a poor outcome and may be candidates for alternative treatment.

Patterns of relapse in large-cell lymphoma patients with bulk disease: implications for the use of adjuvant radiation therapy.

In patients with large-cell lymphoma (LCL) treated with combination chemotherapy, the presence of bulk disease has consistently been associated with a poorer response rate and a shortened survival. The optimal therapy for patients with bulk disease (greater than or equal to 10 cm) will depend on whether treatment failures result from inadequate tumor eradication in prior bulk sites or from distant dissemination. To address this issue, we have evaluated patterns of relapse in patients with bulk disease who relapsed after achieving a complete remission with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M- or m-BACOD). Eighty-one II, III, or IV patients with disease greater than or equal to 10 cm were identified; 45 of the 81 patients achieved a confirmed complete response (CR) and are included in the analysis. The 45 complete responders included 21 patients with localized (stage II) disease and 24 patients with advanced (stage III/IV) disease. Six of the 21 stage II complete responders and three of the 24 stage II/IV complete responders also received adjuvant radiation therapy following completion of M- or m-BACOD. Only one of the 21 patients with stage II disease relapsed, doing so in the site of prior bulk involvement. In contrast, nine of 24 patients with stage III/IV disease relapsed, although no patient failed solely in the site of prior bulk disease. Stage III/IV patients recurred in either a new site (one patient), a new and old site (five), an old non-bulk site (two), or both old non-bulk and bulk sites (one). These results indicate that advanced-stage bulk-disease patients do not consistently relapse in sites of prior bulk disease; therefore, this group of patients is unlikely to benefit from adjuvant radiation therapy administered following completion of combination chemotherapy. Although the low relapse rate and the addition of adjuvant radiation therapy in a subgroup of the stage II bulk-disease patients precludes a definitive analysis, our results further suggest that these patients may be effectively treated with combination chemotherapy alone.

Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting.

The Ann Arbor classification for describing the stage of Hodgkin's disease at initial presentation has formed the basis upon which treatment is selected and has allowed comparison of results achieved by different investigators for almost two decades. A meeting was convened to review the classification and modify it in the light of experience gained in its use and new techniques for evaluating disease. It was concluded that the structure of the classification be maintained. It was particularly recommended: (1) that computed tomography (CT) be included as a technique for evaluating intrathoracic and infradiaphragmatic lymph nodes; (2) that the criteria for clinical involvement of the spleen and liver be modified to include evidence of focal defects with two imaging techniques and that abnormalities of liver function be ignored; (3) that the suffix 'X' to designate bulky disease (greater than 10 cm maximum dimension) be introduced; and (4) that a new category of response to therapy, unconfirmed/uncertain complete remission (CR[u]), be introduced to accommodate the difficulty of persistent radiological abnormalities of uncertain significance.

Mantle irradiation alone for selected patients with laparotomy-staged IA to IIA Hodgkin's disease: preliminary results of a prospective trial.

PURPOSE: To determine the feasibility of omitting prophylactic paraaortic irradiation in selected patients with laparotomy-staged (pathologically staged [PS]) IA to IIA Hodgkin's disease. PATIENTS AND METHODS: We initiated a prospective single-arm trial in October 1988 to study the role of mantle irradiation alone in selected PS IA to IIA patients with Hodgkin's disease. A total of 37 patients have been entered onto this trial. Entrance criteria included nodular sclerosis (NS) or lymphocyte predominance (LP) histology, absence of B symptoms, disease limited above the carina, and a negative laparotomy. Results of treatment of 23 patients in the prospective trial, monitored off treatment for > or = 1 year, are presented. Twenty-three additional PS IA to IIA patients, treated with mantle irradiation alone from 1970 to 1987, were analyzed as a comparison group. The median follow-up durations were 32 and 113 months, respectively, for the two groups. RESULTS: The 4-year actuarial rates of freedom from relapse and overall survival are 83% and 100%, respectively, for the prospective trial. The 10-year actuarial rates of freedom from relapse and overall survival are 83% and 89%, respectively, for retrospectively studied patients. There have been five recurrences among 46 patients who received mantle irradiation alone, all with a component of relapse below the diaphragm. CONCLUSION: These early results support the use of mantle irradiation alone in selected PS IA to IIA patients with NS or LP histology. Relapses, although rare, have occurred predominantly below the diaphragm. This suggests the need for continued long-term surveillance of abdominal and pelvic nodes in this group of treated patients.

The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen.

One hundred thirty-four assessable patients with stage II-IV large-cell lymphoma (LCL) were treated with the combination chemotherapy regimen methotrexate with leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) between July 1981 and May 1986. The m-BACOD regimen substituted moderate-dose methotrexate (200 mg/m2 x 2) for the high-dose methotrexate used in the preceding M-BACOD regimen; all other drugs were administered as with m-BACOD. Eighty-two patients (61%) in the completed m-BACOD trial achieved a complete response (CR). With a median follow-up of 3.6 years, 62 patients (76%) continue in CR. Predicted survivals of 1, 3, and 5 years for the entire m-BACOD group are 80%, 63%, and 60%, respectively, with a 5-year disease-free survival (DFS) of 74% for the patients who achieve CR. The results obtained with m-BACOD are comparable with those obtained in the preceding M-BACOD trial, which now has a median follow-up of 8.0 years. The reduction in methotrexate dosage in m-BACOD patients was not associated with an increased incidence of CNS relapse. Long-term follow-up of the 215 M/m-BACOD patients indicates that the regimens are not associated with an increased incidence of secondary malignancy. Prolonged follow-up also indicates that advanced-stage patients have a persistent rate of late relapse of about 7.0% per year for years 2 to 5 of their follow-up and that stage II patients have an approximate 2.1% per year rate of late relapse. Application of the previously described prognostic factor model to the 215 M/m-BACOD patients from the completed trials identifies a high-risk group of patients with a CR rate and predicted 5-year survival (38% and 24%, respectively) that are significantly worse than those of the group as a whole (65% and 57%, respectively).

Gallium-67 imaging: a predictor of residual tumor viability and clinical outcome in patients with diffuse large-cell lymphoma.

Durable complete remissions (CRs) can be achieved in patients with diffuse large-cell lymphoma (DLCL) with multidrug chemotherapy. The length of time to reach CR may be predictive of treatment outcome. However, defining CR by chest radiograph or computed tomography (CT) is often difficult since residual abnormalities do not always indicate residual disease. We have prospectively evaluated the ability of gallium-67 citrate (Ga-67) imaging to define residual disease and predict outcome in 37 consecutive patients with DLCL. Patients received 296 to 370 megabecquerels (MBq) Ga-67 and were imaged prior to, following cycles 4 to 6, and at completion of intensive chemotherapy. Ga-67 scan results were correlated with radiographic studies. Seventeen of 37 patients (46%) showed persistent, abnormal Ga-67 uptake halfway through chemotherapy. Of these, four were in CR, 11 were in partial remission (PR), and two showed no change in tumor size. At follow-up, 10 (59%) have died (three who were scored as CR and seven who were in PR halfway through therapy), two are alive with active tumor, one relapsed and survives following bone marrow transplant, and four (three in PR and one in CR at the therapeutic halfway point) are without disease at a median of 28 months from presentation. Of the 20 patients who were Ga-67-negative halfway through therapy, 11 were in CR and nine were in PR. Five of 20 patients (25%) have died. Three, in radiographic CR died at 11, 26, and 28 months, and two in radiographic PR died at 15 and 17 months. One patient is alive with active tumor, and 14 patients (70%) are alive without disease at a median of 34 months from presentation. Ga-67 imaging proved to be an excellent indicator of residual viable tumor; a positive scan halfway through therapy predicted for a poor outcome and may well justify a change in treatment.

Effect of megestrol acetate on quality of life in a dose-response trial in women with advanced breast cancer. The Cancer and Leukemia Group B.

PURPOSE: The impact of the side effects of megestrol acetate on the quality of life of noncachectic women with advanced breast cancer was studied in a dose-response clinical trial of the Cancer and Leukemia Group B (CALGB 8741). Side effects of appetite increase and weight gain at higher doses were predicted to have a negative effect on quality of life. PATIENTS AND METHODS: Stage IV breast cancer patients were randomized to receive either 160, 800, or 1,600 mg/d of megestrol acetate. Quality of life was assessed in 131 patients at trial entry and at 1 and 3 months while on treatment, by telephone interview, using the following measures: the Functional Living Index-Cancer (FLIC), Rand Functional Limitations Scale, Rand Mental Health Inventory (MHI), the Body Image Subscale, and linear analog scales of drug side effects. RESULTS: At 3 months, women treated with 160 mg/d reported less severe side effects (P < .0005), better physical functioning (FLS, P < .0005), less psychologic distress (MHI, P = .008), and an improvement in overall quality of life (FLIC, P = .003) from the time of study entry as compared with those treated with 1,600 mg/d. Patients who received the 800-mg/d dose fell between the low- and high-dose arms in reported intensity of drug side effects, but responded similarly to those in the 160-mg/d group in terms of physical functioning, psychologic distress, and overall quality of life. CONCLUSION: Unless additional follow-up data demonstrate a survival advantage at higher doses, the 160-mg/d dose is optimal, achieving maximal treatment effect with the fewest side effects and better quality of life.