Treatment of advanced-stage massive mediastinal Hodgkin's disease: the case for combined modality treatment.

1991 ◽  
Vol 9 (2) ◽  
pp. 227-235 ◽  
Author(s):  
D L Longo ◽  
A Russo ◽  
P L Duffey ◽  
S M Hubbard ◽  
E Glatstein ◽  
...  

In the initial series of 198 patients treated at the National Cancer Institute (NCI) with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy for Hodgkin's disease, a review of presenting chest radiographs available on 192 of these patients showed 49 patients with mediastinal masses greater than one third the greatest posteroanterior chest diameter. Five patients had stage IIB disease, and 44 had stage III or IV disease. Thirty-five (71%) patients achieved a complete remission with MOPP chemotherapy. Fourteen (40%) of the complete responders relapsed, but four of these achieved durable remissions in response to subsequent therapy. Thirty (61%) patients have died (14 induction failures, nine relapsed patients, seven complete responders in remission). Thus, with a median follow-up of 20 years (range, 15 to 23), the overall survival for the group is 39%, and the disease-free survival for the complete responders is 60%. A subset of 10 patients received mantle radiation therapy after maximal response to MOPP. One of these patients failed to achieve complete remission, but among the nine complete responders only one has relapsed. In contrast, 13 of 26 (50%) patients achieving a complete response to MOPP alone have relapsed (P2 = .0536). Although MOPP alone was not prospectively compared with MOPP plus radiation therapy in the treatment of advanced-stage massive mediastinal Hodgkin's disease in this series, the retrospective analysis shows a nearly significant difference in disease-free survival favoring combined modality treatment. The difference in tumor mortality between MOPP-treated (44%) and combined modality-treated patients (80%) was also nearly significant (P2 = .055). However, overall survival differences between patients treated with MOPP alone and those treated with combined modality therapy were not significantly different (P2 = 0.23) because of the mortality related to late complications of combined modality treatment.

1991 ◽  
Vol 9 (8) ◽  
pp. 1409-1420 ◽  
Author(s):  
D L Longo ◽  
P L Duffey ◽  
V T DeVita ◽  
P H Wiernik ◽  
S M Hubbard ◽  
...  

One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS). The median follow-up is 7.7 years. The complete response rate was 60 of 66 MOPP-treated patients (91%) and 54 of 59 MOPP/CABS-treated patients (92%) (difference not significant). The level of the disease-free survival curve at longest follow-up is 65% for MOPP-treated patients and 72% for MOPP/CABS-treated patients (difference not significant). The overall survival at 12 years is projected at 68% for MOPP-treated patients and 54% for MOPP/CABS-treated patients (difference not significant). Thus, there were no significant differences in efficacy between MOPP and MOPP/CABS. However, MOPP/CABS was more emetogenic than MOPP, and four MOPP/CABS-treated patients went on to develop secondary acute leukemia. No MOPP-treated patients developed leukemia. High initial erythrocyte sedimentation rate (ESR) and high platelet counts adversely affected treatment outcome. MOPP-treated patients who received greater than 81% of the projected dose intensity of vincristine over the first three cycles had significantly improved disease-free survival rates over those receiving less than 81%. MOPP/CABS-treated patients who received greater than 82% of the projected dose intensity of vincristine had significantly better overall survival than those who received less than 82%. Disease-free survival on both arms was significantly better in patients who received greater than 84% of the projected dose intensity of all agents. The effect of dose intensity was particularly apparent in patients with poor prognostic factors where those who received greater than 84% of the projected dose intensity of all agents had significantly improved disease-free and overall survival.


1997 ◽  
Vol 15 (11) ◽  
pp. 3338-3346 ◽  
Author(s):  
D L Longo ◽  
E Glatstein ◽  
P L Duffey ◽  
R C Young ◽  
D C Ihde ◽  
...  

PURPOSE To evaluate the efficacy and toxicity of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy plus mantle-field radiation therapy in the treatment of patients with massive mediastinal Hodgkin's disease of any stage. PATIENTS AND METHODS Eighty patients presented with Hodgkin's disease and a mediastinal mass greater than one third the greatest chest diameter on chest radiograph. Patients were staged and treated with MOPP alternated with ABVD chemotherapy for a total of six cycles. Patients then received 10 Gy mantle-field radiation therapy delivered to the original extent of disease followed by 25 to 35 Gy to the residual abnormalities. RESULTS The complete response (CR) rate was 89%. With a median follow-up duration of 10 years, disease-free survival of the complete responders is 78% at 15 years and overall survival is 75% at 15 years. For patients with stage I or II disease, disease-free survival was 76% at 15 years and overall survival was 79%; for those with stage III or IV disease, disease-free survival was 82% at 15 years and overall survival was 64%. Age, stage, sex, B symptoms, number of extranodal sites, lactate dehydrogenase (LDH) levels, erythrocyte sedimentation rate, and platelet count did not influence treatment outcome. Treatment-related pneumonitis was noted in 16% of patients (fatal in one), mainly in those older than age 35 years who received total doses of radiation therapy greater than 42 Gy. Fertility is more often preserved with MOPP/ABVD therapy than with MOPP chemotherapy and there appears to be less pulmonary and cardiac disease than with ABVD chemotherapy. Two patients have developed second solid tumors within radiation ports and one relapsed patient developed acute leukemia after MOPP salvage therapy. CONCLUSION MOPP/ABVD followed by mantle-field radiation therapy is an effective treatment for all stages of Hodgkin's disease that present with a large mediastinal mass. Our data suggest that the large mediastinal mass is a more dominant determinant of prognosis than Ann Arbor stage or other clinical prognostic factors.


1986 ◽  
Vol 4 (6) ◽  
pp. 838-846 ◽  
Author(s):  
V Vinciguerra ◽  
K J Propert ◽  
M Coleman ◽  
J R Anderson ◽  
L Stutzman ◽  
...  

A randomized clinical trial of combination chemotherapy for patients who relapsed following primary radiation therapy for Hodgkin's disease was conducted from 1975 to 1981 by the Cancer and Leukemia Group B (CALGB). One hundred thirteen patients were prospectively randomized to receive 12 cycles of either CVPP (CCNU, vinblastine, procarbazine, and prednisone), ABOS (bleomycin, vincristine [Oncovin; Lilly, Indianapolis], doxorubicin [Adriamycin, Adria Laboratories, Columbus, Ohio], and streptozotocin), or alternating cycles of CVPP and ABOS. The median length of observation for patients in this report is 4 years. Toxicities of the three treatment programs were primarily hematologic. Frequencies of complete response were 72% for CVPP, 70% for ABOS, and 82% for CVPP/ABOS (P = .37). Females and patients who had nodular sclerosing disease at initial diagnosis had significantly higher complete response rates. The 5-year disease-free survival for the complete responders was 55%; the 5-year overall survival was 60%. There were no significant differences among the treatments on disease-free survival (P = .78) or overall survival (P = .18). Age under 40 years was the only significant positive prognostic factor for disease-free survival (P = .095) and overall survival (P = .003). This study demonstrates no statistically significant advantage for alternating cycles of combination chemotherapy in affecting complete response frequency, disease-free survival, or overall survival as compared with therapy with CVPP or ABOS alone. However, the power to detect differences in these outcome parameters is somewhat limited by the sample sizes.(ABSTRACT TRUNCATED AT 250 WORDS)


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1375-1375
Author(s):  
Vishal Kukreti ◽  
Peter Petersen ◽  
Melania Pintilie ◽  
Richard Tsang ◽  
Michael Crump ◽  
...  

Abstract Follicular lymphoma arising in an extranodal site is uncommon and its natural history and treatment is poorly characterized in the literature. We retrospectively reviewed a large cohort of patients with stage I and II follicular lymphoma and analyzed the outcomes of patients with extranodal (EN-FL) presentations to identify sites of involvement and treatment outcome, and compared these to patients with nodal follicular lymphoma. From 1967 to 1999, 668 cases of limited stage follicular lymphoma (stage I and II) were treated at the Princess Margaret Hospital. Of these, 157 cases (23.5%) presented in extra-nodal sites. The most common site of presentation was in the head and neck area (42%) followed by gastro-intestinal tract (14.6%) then skin (10.8%). The majority of patients had stage I disease (61.8%). Pathological type was follicular grade I: 22.9%, grade II: 33.1%, and grade III: 43.9%. Treatment consisted of involved field radiation therapy in 72%, combined modality therapy in 22.3% and chemotherapy alone in 3.8%. The treatment changed over time with increased use of combined modality treatment (CMT) [1967–77: 10.5%, vs. 1989–99: 33%] mainly due to the adoption of CMT for follicular grade III lymphoma. Overall complete response rate (CR) to primary treatment was 93%; the CR rate for radiation alone was 97.3%. The cumulative incidence of relapse (RR) was 44% at 10 years. The RR at 10 years was higher for patients age >60 (62% vs. 49%; p =0.059) but did not vary according to stage, tumour bulk, gender or histologic grade. For extranodal lymphoma, the 10-year overall survival (OS) rate was 56% and the 10-year disease free survival (DFS) was 42% and was similar for major sites of presentation. Comparison of Stage I–II Nodal and Extra-nodal Follicular Lymphoma Nodal Follicular Lymphoma Extra-nodal Follicular Lymphoma 10 yr Overall Survival 61% 56% (p=0.97) 10 year Disease Free Survival 41% 42% (p=0.27) 10 yr Relapse Rate 50% 44% (p=0.11) In conclusion, a significant number of patients with localized FL present with extra-nodal disease, involving diverse sites. Patients with EN-FL were more likely to have follicular grade III histology. OS, DFS and RR were similar to nodal follicular lymphoma. These results suggest that the clinical management of stage I and II extra-nodal follicular lymphoma should be the same as for nodal, and that a significant proportion of patients have prolonged DFS with radiation-based therapy.


2001 ◽  
Vol 19 (3) ◽  
pp. 628-633 ◽  
Author(s):  
Rogelio A. Brito ◽  
Vicente Valero ◽  
Aman U. Buzdar ◽  
Daniel J. Booser ◽  
Frederick Ames ◽  
...  

PURPOSE: To determine outcomes in local-regional control, disease-free survival, and overall survival in patients with locally advanced breast cancer (LABC) who present with ipsilateral supraclavicular metastases and who are treated with combined-modality therapy.PATIENTS AND METHODS: Seventy patients with regional stage IV LABC, which is defined by our institution as LABC with ipsilateral supraclavicular adenopathy without evidence of distant disease, received treatment on three prospective trials of neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil, or cyclophosphamide, doxorubicin, vincristine, and prednisone. Patients then received local therapy that consisted of either total mastectomy and axillary lymph node dissection (ALND) or segmental mastectomy and ALND before or after irradiation. Patients with no response to neoadjuvant chemotherapy were treated with surgery and/or radiotherapy. After completion of local therapy, chemotherapy was continued for four to 15 cycles, followed by radiotherapy. Patients older than 50 years who had estrogen receptor–positive tumors received tamoxifen for 5 years.RESULTS: Median follow-up was 11.6 years (range, 4.8 to 22.6 years). Disease-free survival rates at 5 and 10 years were 34% and 32%, respectively. The median disease-free survival was 1.9 years. Overall survival rates at 5 and 10 years were 41% and 31%, respectively. The median overall survival was 3.5 years. The overall response rate (partial and complete responses) to induction chemotherapy was 89%. No treatment-related deaths occurred.CONCLUSION: Patients with ipsilateral supraclavicular metastases but no other evidence of distant metastases warrant therapy administered with curative intent, ie, combined-modality therapy consisting of chemotherapy, surgery, and radiotherapy. Patients with ipsilateral supraclavicular metastases should be included in the stage IIIB category of the tumor-node-metastasis classification because their clinical course and prognosis are similar to those of patients with stage IIIB LABC.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7708-7708 ◽  
Author(s):  
M. de Perrot ◽  
R. Feld ◽  
M. Anraku ◽  
A. Bezjak ◽  
R. Burkes ◽  
...  

7708 Background: Examine the results of tri-modality therapy for malignant pleural mesothelioma (MPM). Methods: Protocol consisted of induction cisplatin-based chemotherapy, followed by extrapleural pneumonectomy (EPP) and adjuvant hemithoracic radiation therapy (RT) to 54 Gy. Results: A total of 60 patients were suitable candidates for tri-modality therapy between 01/2001 and 01/2007. Induction chemotherapy was administered to 56 patients; 4 patients underwent EPP without induction chemotherapy because of patient refusal (n=2), previous chemotherapy (n=1) and sarcomatoid MPM (n=1). Chemotherapy included vinorelbine/cisplatin (n=26), pemetrexed/cisplatin (n=26) and gemcitabine/cisplatin (n=4). EPP was performed in 47 patients; 13 patients did not undergo EPP because of tumor progression during chemotherapy (n=2), extensive chest wall involvement at surgery (n=6), or involvement of mediastinal lymph nodes at mediastinoscopy (n=5). Three patients (6%) died within 30 days of surgery. Pathological stage was II (n=6), III (n=35), and IV (n=6). Adjuvant RT was administered postoperatively to 36 patients and is ongoing in 5 patients; 6 patients did not receive adjuvant RT because of fatigue (n=5) or previous RT (n=1), and 4 patients did not complete RT up to 54 Gy. Overall survival for the 23 patients who completed the tri-modality therapy was 37% at 3 years with a median survival of 15 months. Eleven of the 23 patients had recurrence after a median of 8 months (range, 2–13 months). Recurrences were locoregional (n=2), in contralateral chest (n=3), abdomen (n=3), contralateral chest and abdomen (n=2), or pericardium (n=1). Among patients undergoing EPP, disease-free survival was longer in patients undergoing adjuvant high dose hemithoracic RT (p=0.07), in epithelial tumors (p=0.03), and in early stage (p=0.07). Overall survival was influenced by histology (p=0.007) and stage (p=0.05), but not by adjuvant high dose hemithoracic RT (p=0.5). The type of chemotherapy had no impact on disease-free and overall survival. Conclusions: Aggressive tri-modality therapy is feasible in selected patient with MPM. Adjuvant high dose hemithoracic RT can improve disease free survival and achieve good local control. No significant financial relationships to disclose.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4581-4581
Author(s):  
Eyad F. Alsaeed ◽  
Rajiv Samant ◽  
Gallant Victor ◽  
Lother Huebsch ◽  
Wayne Kendal

Abstract Introduction The treatment of early stage Hodgkin’s lymphoma is controversial. Radiotherapy alone, chemotherapy alone or a combination of radiotherapy and chemotherapy are all considered effective options. Purpose The purpose of this study is to review the treatment approaches and outcomes used for early stage Hodgkin’s lymphoma over the past two decades at ORCC Methods Retrospective chart review of all patients with stage IA /IIA treated from 1984–2002 was performed. Patients were separated into three groups according to initial treatment modality: radiation alone (Rads), chemotherapy alone (Chemo), or combined modality (Combined). Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis. Result Between May 1984 and January 2003, 172 patients with newly diagnosed Hodgkin’s lymphoma (28% stage 1A, 72% stage 2A) were seen at our centre. Treatment was as follows: 49% Rads, 13% Chemo and 38% Combined. The median age was 33.7 years (range: 17 – 82 years) and the median follow-up of 73 months (range: 3 – 204 months). The 5-year disease free and overall survival rates for the entire group were 90% and 96 % respectively. The 5-year disease-free and overall survival by treatment modality was: Rads 87% and 93 %; Chemo 80 % and 100 %; Combined 97 % and 98%. In the Combined group, there was no difference in outcome between patients receiving involved-field radiation and those receiving extended-field radiotherapy. The relapse rate in a patient who received abbreviated chemotherapy and greater than four cycles was 4.3% (1 out of 23) and 2.4% (1 out of 41) respectively. The incidence of acute Grade 3 and 4 toxicities were 9 % and 0.5% respectively. Conclusions Our data confirms the excellent prognosis of early stage Hodgkin’s lymphoma with all the approaches used at our centre. At present, we favour combined modality treatment with involved-field radiotherapy and our results support its continued use.


1998 ◽  
Vol 16 (3) ◽  
pp. 818-829 ◽  
Author(s):  
M Loeffler ◽  
O Brosteanu ◽  
D Hasenclever ◽  
M Sextro ◽  
D Assouline ◽  
...  

DESIGN To perform a meta-analysis of all randomized trials that compared chemotherapy (CT) alone versus combined modality treatment (CT + radiotherapy [RT]) for which individual patient data could be made available. PATIENTS AND METHODS Data on 1,740 patients treated on 14 different trials that included 16 relevant comparisons have been analysed. Eight comparisons were designed to evaluate the benefit of additional RT after the same CT (CT1 v CT1 + RT; additional RT design). Eight comparisons were designed to evaluate whether RT in a combined modality setting can be substituted by CT using either more cycles of the same CT or regimens that contain additional drugs (CT1 + CT2 v CT1 + RT or CT1 v CT2 + RT; parallel RT/CT design). RESULTS Additional RT showed an 11% overall improvement in tumor control rate after 10 years (P = .0001; 95% confidence interval [CI], 4% to 18%). No difference could be detected with respect to overall survival (P = .57; 95% CI, -10% to 4%). In contrast, when combined modality treatment was compared with CT alone in the parallel-design trials, no difference could be detected in tumor control rates (P = .43; 95% CI, -6% to 9%), but overall survival was significantly better after 10 years in the group that did not receive RT (P = .045; 8% difference; 95% CI, 1% to 15%). There were significantly fewer fatal events among patients in continuous complete remission (relative risk [RR], 1.73; 95% CI, 1.17 to 2.53; P = .005) if no RT was given. CONCLUSION Combined modality treatment in patients with advanced-stage Hodgkin's disease overall has a significantly inferior long-term survival outcome than CT alone if CT is given over an appropriate number of cycles. The role of RT in this setting is limited to specific indications.


Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 562-564 ◽  
Author(s):  
HS Jaffe ◽  
EC Cadman ◽  
LR Farber ◽  
JR Bertino

Pretreatment hematocrit in 117 advanced-stage Hodgkin's disease patients treated with a combined modality therapy program was evaluated as an independent prognostic variable with regard to survival and relapse-free survival. Age greater than 40 years, and multiple extranodal sites of involvement were found to be statistically significant independent negative prognostic factors with regard to survival. Pretreatment hematocrit, however, was not an independent negative prognostic variable.


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