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Prognostic factors for 53 previously untreated patients with Stage IV Hodgkin's disease were analyzed for their effects upon complete remission rate, survival, and disease-free survival following treatment with mechlorethamine, Oncovin (vincristine), procarbazine, and prednisone (MOPP) or MOPP plus bleomycin (MOPP-Bleo). Although 75% of those patients with only one site of extranodal disease achieved complete remission, only 25% of those with more than one site of involvement entered complete remission. Seven of the eight patients with more than one extranodal site were dead of disease at 4 years, compared with a 5-year survival of 75% for those with only one site of involvement. Disease-free survival from complete remission was dependent upon the percentage of planned doses of nitrogen mustard actually administered. Patients who received higher doses of nitrogen mustard had significantly longer freedom from relapse and survival after attaining complete remission than those who received reduced doses. Age, symptoms, pathologic features, and presence or size of mediastinal disease did not affect the couple remission rate, survival, or disease-free survival. Patients with Stage IV disease treated with MOPP alone should receive the highest tolerable dose of nitrogen mustard early in their treatment, since those receiving lower doses have a higher risk of relapse.

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Combined modality therapy consisting of CHOP-Bleo (cyclophosphamide, Adriamycin [doxorubicin], vincristine (Oncovin), prednisone, and bleomycin) and limited-field radiotherapy was given to 47 patients with Stage III and IIIE diffuse large cell lymphomas. Overall 5-year survival and disease-free survival figures are 64% and 53%, respectively. Twenty-nine patients achieved and maintained a complete remission during treatment; 92% of these patients are alive at 5 years, and 87% are disease-free. Prognostic factors were assessed for the entire group. Age, "B" symptoms, extranodal involvement, and extensive abdominal involvement had little effect on survival. However, the presence of mediastinal involvement and extensive abdominal involvement was associated with a poor response rate and survival.

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Since 1975, all histologic subtypes of Stage III and IIIE nodular lymphoma patients were treated with a combination of radiotherapy and multiple-agent chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo). Fifty-eight patients were treated through 1979. Treatment consisted of two cycles of CHOP-Bleo alternating with sequential radiotherapy to clinically involved regions, and further CHOP-Bleo to a total of ten cycles. Radiotherapy doses ranged between 3000 and 4000 rad delivered in three to four weeks. Forty-six patients completed treatment. In the other 12 patients, treatment was interrupted because of progressive disease in seven, and myelosuppression in five. Overall five-year survival and disease-free survival results were 82% and 47%, respectively. Survival for those patients who completed therapy was 93%. By histopathology, survivals for all patients were: poorly differentiated lymphocytic, 100%; mixed cell, 80%; and histiocytic, 39%. Disease-free figures for all 58 patients were: poorly differentiated lymphocytic, 44%; mixed cell, 65%; and histiocytic, 35%. The extent of abdominal disease influenced five-year survival as follows: 100% for those who had only occult disease at staging laparotomy; 88% for those who were Stage III on the basis of a positive lymphangiogram; and 50% for those who had a palpable mass or required an exploratory laparotomy for symptoms. Five of seven patients with progression during protocol therapy have died. No patients died as a result of myelosuppression. A number of patients developed complications during treatment, none of which were fatal. Eight patients developed herpes zoster, four patients developed transient radiation hepatitis, and four patients had miscellaneous complications.

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In this study, 95 patients with laparotomy-staged I and II nonmediastinal Hodgkin's disease were treated with involved fields (41 patients), mantle (17), extended fields (26), or involved fields followed by 6 cycles of MOPP (11). Eighty-five patients had upper torso presentations. Seventy had Stage I disease and 25 had stage II. Pathologic findings were nodular sclerosing, 33; mixed cellularity, 41; lymphocyte predominance, 20; and unclassified, one. Five-year overall survivals were excellent regardless of stage, pathologic findings, or treatment: 98% for involved fields or mantle, and 100% for both extended fields and involved fields followed by 6 cycles of MOPP. Corresponding disease-free survivals were 77%, 82%, and 86%, respectively. For patients with upper torso presentations, disease-free figures for the mantle (94%) were better than those for involved fields alone (67%). In addition, regression analysis proved involved fields to be a prognostic factor for a lower disease-free survival. No difference between extended fields or mantle radiotherapy could be detected using this model. Relapses usually occurred in nonirradiated upper torso sites. Only three of the 36 patients treated with involved fields and one of 21 treated with extended fields relapsed in the abdomen alone. Most patients in relapse were salvaged. Rescue treatment was most often radiotherapy and adjuvant combination chemotherapy. Based on this study, the use of mantle radiotherapy is recommended in treating laparotomy-staged I and II patients with nonmediastinal presentations, and the use of extended fields or adjuvant chemotherapy as primary prevention is not recommended.

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A retrospective study of 75 laparotomy-studied Stage I and II patients with diffuse large cell (histiocytic) lymphoma was conducted to determine the relative contributions of laparotomy, radiotherapy, and combination chemotherapy to their management. The treatment programs were radiotherapy alone, radiotherapy followed by adjuvant chemotherapy, and alternating chemotherapy-radiotherapy. Treatment selection was based on disease presentation, with limited therapy used for favorable patterns and intensive therapy used in prognostically unfavorable settings. Disease-free survival was best in those treated with initial chemotherapy, even though these patients comprised the least favorable prognostic group. A select subset of patients, those with extranodal head and neck disease, obtained good results with radiotherapy alone, but for other presentations this was not a successful approach. Differences in results for the three treatment programs are discussed in relation to future treatment decisions.

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The importance of initial mediastinal disease was studied retrospectively in 189 patients with stages I, II, and III Hodgkin disease treated at the M. D. Anderson Hospital and Tumor Institute between 1969 and 1976. Stages I and II patients with mediastinal disease at presentation had an 88% 5 year survival rate compared with a 98% survival rate for those without mediastinal disease. Disease-free survival was 66% versus 78%. Stage III patients with and without initial mediastinal disease showed essentially the same 5 year survival rate (75% versus 78%), but showed a lower disease-free survival of 60% in those with mediastinal disease as compared with 74% in those without mediastinal disease. Because of the prognostic importance of mediastinal disease and its extent at initial presentation, computed tomography is recommended to evaluate patients with low neck or supraclavicular adenopathy in whom there is no obvious mediastinal adenopathy and in all Hodgkin disease patients in whom there is questionable mediastinal disease or suggestion of lung extension on routine radiographs. Treatment plans have been altered to include chemotherapy and low-dose irradiation to the lungs in those patients with mediastinal mass diameters of 7.5 cm or greater, regardless of stage.

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Three treatment programs for Stage I and II mediastinal Hodgkin disease (established by laparotomy) were compared. Involved-field radiotherapy + MOPP gave a disease-free survival rate of 97%, significantly different from 62% and 55% for involved and extended fields, respectively. Corresponding survival figures of 97%, 88%, and 84% were not significantly different statistically due to salvage with radiotherapy and/or chemotherapy. Among patients given radiotherapy alone, the survival figure of 94% for limited mediastinal disease was significantly better than 63% for extensive mediastinal and hilar disease; corresponding disease-free figures of 72% and 35% were also significantly different. Constitutional symptoms were an important prognostic factor in disease-free survival following the use of involved fields; hilar disease was important only with large mediastinal masses. Most relapses were intrathoracic; MOPP alone salvaged only 47%. Treatment of Stage I and II Hodgkin disease should be based on symptoms, extent of mediastinal disease, and hilar involvement.

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Prognostic factors have been re-evaluated for 88 patients with Stage III Hodgkin's disease to see if they have remained significant on a long-term basis. Treatment had consisted of two cycles of MOPP followed by radiotherapy to the mantle, abdomen, and pelvis; all patients had achieved complete remission. Case material was grouped according to the presence of absence of mediastinal disease. Five-year survivals for Stage IIIA and IIIB patients were 85 and 80%; corresponding disease-free survivals were 76 and 73%. Significant prognostic factors include age, histopathology, and extent of abdominal disease, but the relative importance of these factors differs for the mediastinal and nonmediastinal patients. Modifications of current treatment policy for both mediastinal and nonmediastinal patients are discussed in relation to the prognostic factors.

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ABDIC was administered to 32 patients with MOPP-resistant Hodgkin's disease. Three were considered nonevaluable because of early death. All patients had received MOPP (medium of eight cycles), and five had also received other chemotherapy. Major radiotherapy had been used in 18 of the 29. Complete remission (CR) occurred in 10 of 29 (34.5%), partial remissions (PR) in 14 (48.2%), and no remissions (NR) in five (17.2%). Median survival and relapse-free survival for CR patients exceeded 28 months. Two relapsed at 8 and 18 months; one died at 9 1/2 months, and the other is disease-free with other treatment at 35 months. Seven of the remaining eight patients are alive without disease (10-35 months); 4 are on maintenance therapy, and the other died from an infection and eosinophilic granuloma of lung without evidence of recurrent Hodgkin's disease. Median survival of PR patients was eight months. One patient with Hodgkin's disease involving the liver is alive at 36 months with further therapy. Median survival of NR patients is 2.5 months, and all died within seven months. Survival of CR patients is greater than PR and NR patients (P = 0.002), and that of PR is greater than NR (P = 0.01). Four of the 29 patients had nodal relapse, and 25 had parenchymal relapse, with no difference in response rates (P = 0.47). ABDIC is useful in Hodgkin's disease patients who have had extensive prior chemotherapy and radiotherapy.

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Ninety patients with Stage I or II, including extranodal (E), presentations of non-Hodkin's lymphoma were investigated by laparotomy, either for the definitive staging of patients with peripheral presentations or for diagnosis of abdominal disease. Sixty-eight patients had staging laparotomies after extensive work-up, which included lymphangiography and bone marrow biopsy. The remaining 22 patients had laparotomies for diagnosis of abdominal symptoms or for management of unrelated surgical problems, with lyphoma being found incidentally. The incidence of positive abdominal findings in the 68 patients who had staging laparotomies depended on histologic subtype. In nodular lymphoma patients, abdominal disease was found in 17 of 28 (61%) and in diffuse lymphoma patients, in 9 of 40 (22.5%). For patients with nodular lymphomas upstaged by laparotomy, the positive findings tended to cluster around an axis consisting of the celiac, porta-hepatic, para-aortic, and root of the mesentery lymph nodes. In addition, 64% of these patients had splenic involvement. For the diffuse lymphoma upstaged by laparotomy, the distribution of positive findings was similar to that of the nodular lymphoma group; however, only 1 patient had splenic involvement. By contrast, in approximately half of the diffuse lymphoma patients who had laparotomies for diagnosis, the gastrointestinal tract was found to be involved in addition to the previously cited lymph nodes.

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One hundred consecutive Stage IIIA and IIIB Hodgkin's disease patients were treated between July 1969 and September 1976, on a combined chemotherapy-radiotherapy program consisting of two courses of MOPP followed by radiotherapy to the mantle, abdomen, and pelvis. Eighty-eight patients completed radiotherapy to all disease sites. At the time of this analysis, the mean follow-up period for the 100 patients was 45 months; 70 patients had been followed three to seven years. Projected five-year survival and disease-free survival figures for the 100 patients were 80% and 68% respectively; corresponding results for the 88 patients were 90% and 78%. To determine whether any of the following prognostic factors influenced results for either the 100 or the 88 patients, survival curves were calculated for age, sex, constitutional symptoms, histopathology, method of staging, and status of the mediastinum. Other than age, none of these factors influenced survival significantly. However, disease-free survival figures were influenced adversely by mediastinal disease as well as age.

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Fifty-three non-Hodgkin's lymphoma patients staged I, IE, II, and IIE after laparotomy, received involved field radiotherapy with or without adjunctive chemotherapy. These cases have been analyzed for survival, disease-free survival, sites of relapse, and subsequent management. For nodular lymphoma patients, the five-year survival figure was 87%. While this represents only modest improvement over survival figures for patients staged I and II by lymphangiography, results for patients with upper torso disease were significantly better. Although there was a definite incidence of relapse, early failures common in the lymphangiogram series, were not seen in this study. Of the total group of 14 patients, 4 relapsed after a minimum complete remission period of 20 months. The five-year survival figure for all presentations of stages I and II diffuse histiocytic lymphoma was 85%. This represents a substantial improvement over the corresponding figure of 36% for patients staged clinically after lymphangiography. The improvement in results is credited to more precise staging of patients with peripheral presentations, the use of adjunctive multiple-agent chemotherapy for abdominal and mediastinal presentations, and more effective treatment for relapse. To date, too few patients with peripheral presentations have been treated to determine the value of adjunctive chemotherapy for nodular or diffuse histiocytic patients.

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The electrocardiograms of 146 patients with metastatic carcinoma of the breast were reviewed before, during, and after the patients received Adriamycin (Doxorubicin) chemotherapy (AD). The most significant electrocardiographic change occurred in the amplitude of the QRS voltage. Seven patients developed cardiomyopathy after AD and showed a significant decrease in QRS voltage. This decrease, however, was more severe at the onset of congestive heart failure that at conclusion of Adriamycin. In 35 patients with pleural effusion, there was an inverse relation between the extent of the effusion and the amplitude of QRS voltage in the absence of congestive heart failure. These results indicate that 1) the sudden and relatively severe decrease in QRS voltage with the onset of CHF limits the value of this ECG criterion for predicting early Adriamycin toxicity, and 2) caution should be exercised in the interpretation of QRS voltage changes in patients with significant pleural effusion.

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A detailed review of our results of radiotherapy for stage I and II non-Hodgkin's lymphomas has been presented as background for our current multidisciplinary approach which uses multiple-agent chemotherapy, radiotherapy, and immunotherapy for nodular and diffuse stage I, II, and III lymphomas of the poorly differnetiated lymphocytic, mixed, and histiocytic varieties. Optimum management is based on coordinated efforts of medicine, radiotherapy, pathology, diagnostic radiology, and surgery. In stage I, II, and III disease, routine staging procedures include lymphangiography, bilateral iliac crest needle biopsies of the bone marrow, and percutaneous needle biopsies of the liver. Staging laparotomy is considered essential to our present program for stage I, IE, II and IIE disease. In our opinion, staging laparotomy is not indicated in stage II or IIIE disease. Although very preliminary, results for these programs are encouraging. This paper presents the concept of team management and a specific plan for its implementation.

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Analysis of regional pulmonary function distribution using radioactive 133xenon gas and eight scintillation detectors was performed in a patient with scimitar syndrome. Zonal ventilation per unit of lung volume within the slightly hypoplastic right lung was normal. The pulmonary blood flow to the lower right zone was significantly reduced due to aberrant systemic arterial supply to the right lower lobe. The 133xenon technique provides a simple nontraumatic method of evaluating the functional integrity of the right lung in this cardiopulmonary syndrome.

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Pericardial effusion and trifascicular block developed 5 years following mediastinal irradiation for Hodgkin's disease in a 19-year-old patient. Another 24-year-old patients had an acute myocardial infarction followed by severe angina pectoris 5 years following mediastinal irradiation for the same disease. A pericardial window and a permanent demand pacemaker were used in the first case; an aorto-coronary vein grafting was utilized in the second patient. Both patients responded to treatment and are well. Five other previously reported cases of myocardial injury that occurred 2 months to 8 years following mediastinal irradiation in young patients were reviewed. To our knowledge, successful surgical treatment of this disease entity has not been reported before. Close, long-term follow-up of patients who have received mediastinal irradiation should be helpful in the early recognition and successful management of these serious cardiac complications. The systematic clinical and radiographic surveilance of these patients should be supplemented by a routine 12-lead electrocardiogram.

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