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Background: Long-term survivors of non-Hodgkin lymphoma (NHL) must cope with treatment complications and late toxicities that affect their health-related quality of life. Little is known about the risk-to-benefit ratio of new agents like rituximab. The impact of treatment regimens and health disorders on long-term fatigue levels was investigated in a cross-sectional study., Methods: Two self-administered questionnaires, the 20-item Multidimensional Fatigue Inventory (MFI-20) and a Life Situation Questionnaire, were mailed in 2015 to NHL survivors enrolled onto 12 successive clinical studies (1993-2010) conducted by the Lymphoma Study Association. Private addresses were obtained for 3317 survivors, of whom 1671 (50%) returned the questionnaires. Severe fatigue was defined as MFI-20 scores ≥60 on dimension scales scored from 0 to 100. Linear regression models were used to assess factors that were linked to increased fatigue levels., Results: The study population included 906 men and 765 women, and the median age was 64 years (age range, 24-95 years). Overall, 811 survivors had received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-like chemotherapy, 518 had received high-dose CHOP, and 342 had undergone upfront autologous stem cell transplantation; 829 survivors also had received rituximab. In total, 1100 survivors (66%) reported 1 or more late health disorders. Severe fatigue was reported by 602 survivors (37%). Increased fatigue levels were associated (P < .001) with increased age, obesity, and the presence of health disorders, but not with initial treatment or rituximab., Conclusions: The survey confirms that high proportions long-term NHL survivors have severe fatigue. The results suggest that initial treatment and the receipt of rituximab have no influence on the development of long-term fatigue., (© 2019 American Cancer Society.)

Purpose: While patients with early-stage Hodgkin lymphoma (HL) have an excellent outcome with combined treatment, the radiation therapy (RT) dose and treatment with chemotherapy alone remain questionable. This noninferiority trial evaluates the feasibility of reducing the dose or omitting RT after chemotherapy., Methods and Materials: Patients with untreated supradiaphragmatic HL without risk factors (age ≥ 50 years, 4 to 5 nodal areas involved, mediastinum-thoracic ratio ≥ 0.35, and erythrocyte sedimentation rate ≥ 50 mm in first hour without B symptoms or erythrocyte sedimentation rate ≥ 30 mm in first hour with B symptoms) were eligible for the trial. Patients in complete remission after chemotherapy were randomized to no RT, low-dose RT (20 Gy in 10 fractions), or standard-dose involved-field RT (36 Gy in 18 fractions). The limit of noninferiority was 10% for the difference between 5-year relapse-free survival (RFS) estimates. From September 1998 to May 2004, 783 patients received 6 cycles of epirubicin, bleomycin, vinblastine, and prednisone; 592 achieved complete remission or unconfirmed complete remission, of whom 578 were randomized to receive 36 Gy (n=239), 20 Gy of involved-field RT (n=209), or no RT (n=130)., Results: Randomization to the no-RT arm was prematurely stopped (≥20% rate of inacceptable events: toxicity, treatment modification, early relapse, or death). Results in the 20-Gy arm (5-year RFS, 84.2%) were not inferior to those in the 36-Gy arm (5-year RFS, 88.6%) (difference, 4.4%; 90% confidence interval [CI] -1.2% to 9.9%). A difference of 16.5% (90% CI 8.0%-25.0%) in 5-year RFS estimates was observed between the no-RT arm (69.8%) and the 36-Gy arm (86.3%); the hazard ratio was 2.55 (95% CI 1.44-4.53; P<.001). The 5-year overall survival estimates ranged from 97% to 99%., Conclusions: In adult patients with early-stage HL without risk factors in complete remission after epirubicin, bleomycin, vinblastine, and prednisone chemotherapy, the RT dose may be limited to 20 Gy without compromising disease control. Omitting RT in these patients may jeopardize the treatment outcome., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: For early-stage Hodgkin lymphoma (HL), optimal chemotherapy regimen and the number of cycles to be delivered remain to settle down. The H9-U trial compared three modalities of chemotherapy followed by involved-field radiotherapy (IFRT) in patients with stage I-II HL and risk factors (NCT00005584)., Patients and Methods: Patients aged 15-70 years with untreated supradiaphragmatic HL with at least one risk factor (age ≥ 50, involvement of 4-5 nodal areas, mediastinum/thoracic ratio ≥ 0.35, erythrocyte sedimentation rate (ESR) ≥ 50 without B-symptoms or ESR ≥ 30 and B-symptoms) were eligible for the randomised, open label, multicentre, non-inferiority H9-U trial. The limit of non-inferiority was set at 10% for the difference between 5-year event-free survival (EFS) estimates. From October 1998 to September 2002, 808 patients were randomised to receive either the control arm 6-ABVD-IFRT (n = 276), or one of the two experimental arms: 4-ABVD-IFRT (n = 277) or 4-BEACOPP baseline -IFRT (n = 255)., Results: Results in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPP baseline -IFRT (5-year EFS, 88.8%) were not inferior to 6-ABVD-IFRT (5-year EFS, 89.9%): difference of 4.0% (90%CI, -0.7%-8.8%) and of 1.1% (90%CI,-3.5%-5.6%) respectively. The 5-year overall survival estimates were 94%, 93%, and 93%, respectively. Patients treated with combined modality treatment chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vincristine (Oncovin), cyclophosphamide, procarbazine, etoposide and prednisone (BEACOPP) baseline more often developed serious adverse events requiring supportive measures and hospitalisation compared with patients receiving the chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD)., Conclusions: The trial demonstrates that 4-ABVD followed by IFRT yields high disease control in patients with early-stage HL and risk factors responding to chemotherapy. Although non-inferior in terms of efficacy, four cycles of BEACOPP baseline were more toxic than four or six cycles of ABVD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the efficacy of pegylated liposomal doxorubicin (PLD) and continuous infusion ifosfamide (IFO) in ovarian cancer patients who relapse within 1 year after first-line paclitaxel-platinum-based chemotherapy., Methods: Patients were stratified according to treatment-free interval (TFI) (or=6 months). PLD (40 mg/m(2), day 1), IFO (1700 mg/m(2), infusion days 1-3), and mesna were given every 28 days for 6-9 cycles. Primary endpoint was objective response rate (ORR). Secondary endpoints were response duration, progression free survival (PFS), overall survival (OS), and toxicity., Results: There were 98 evaluable patients (58%, TFI<6 months). Median number of cycles was 5 (range: 1-9). The frequency of grade 3/4 anemia, thrombocytopenia, and neutropenia was 7%, 3%, and 48%, respectively; febrile neutropenia was 3%. A low rate of grade 3/4 non-hematologic toxicities was reported, including nausea/vomiting (3/4%), hand-foot syndrome (2%), and mucositis (2%). The ORR was 28% (41% and 19% in patients with TFI >or=6, or <6 months, respectively); rate of disease stabilization was 26%; response duration and median OS were 6 (2.4-26) and 14 (1-46) months, respectively., Conclusion: The combination of PLD and continuous IFO is a feasible and efficient treatment in patients with relapsed ovarian cancer, especially with TFI between 6 and 12 months. This regimen may represent an alternative to platinum reintroduction and should be evaluated in a randomized trial.

Objectives: The aim of this phase II study was to assess the benefits of a weekly administration of topotecan and gemcitabine in patients with ovarian carcinoma having relapsed after platinum/taxane-based first-line chemotherapy., Methods: Seventy-seven patients with progression of disease /=2 cycles administered). The only major severe toxicity was neutropenia grades 3 (17%) and 4 (6%). Approximately 60% of the patients received the complete schedule of treatment, dose interruptions/delays being mainly due to moderate thrombocytopenia or neutropenia. The objective response rate was 14%, the values for patients having relapsed within 6 (n=30) and 6-12 (n=36) months being 7% and 20%, respectively. Median durations of response were 4.9 and 6.4 months and clinical benefit rates including stabilizations reached 63% and 69% in patients having relapsed within 6 or 6-12 months, respectively. Corresponding median overall survival was 7.5 and 15.6 months. Symptoms and pain were reduced in 64% and 39% of the patients concerned, respectively., Conclusion: In early relapse ovarian cancer, weekly combination of gemcitabine and topotecan has a modest objective response rate. However, a high proportion of patients experienced stable disease and symptom control leading to acceptable quality of life.

Background: Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure., Methods: From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin's disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy (reference group), four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy., Results: The median follow-up was 92 months. In the H8-F trial, the estimated 5-year event-free survival rate was significantly higher after three cycles of MOPP-ABV plus involved-field radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P<0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P=0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involved-field radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively., Conclusions: Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (ClinicalTrials.gov number, NCT00379041 [ClinicalTrials.gov].)., (Copyright 2007 Massachusetts Medical Society.)

Purpose: The use of radiotherapy in patients with advanced Hodgkin's lymphoma (HL) is controversial. The purpose of this study was to describe the role of radiotherapy in patients with advanced HL who were in partial remission (PR) after chemotherapy., Methods: In a prospective randomized trial, patients <70 years old with previously untreated Stage III-IV HL were treated with six to eight cycles of mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycine, vinblastine hybrid chemotherapy. Patients in complete remission (CR) after chemotherapy were randomized between no further treatment and involved-field radiotherapy (IF-RT). Those in PR after six cycles received IF-RT (30 Gy to originally involved nodal areas and 18-24 Gy to extranodal sites with or without a boost)., Results: Of 739 enrolled patients, 57% were in CR and 33% in PR after chemotherapy. The median follow-up was 7.8 years. Patients in PR had bulky mediastinal involvement significantly more often than did those in CR after chemotherapy. The 8-year event-free survival and overall survival rate for the 227 patients in PR who received IF-RT was 76% and 84%, respectively. These rates were not significantly different from those for CR patients who received IF-RT (73% and 78%) or for those in CR who did not receive IF-RT (77% and 85%). The incidence of second malignancies in patients in PR who were treated with IF-RT was similar to that in nonirradiated patients., Conclusion: Patients in PR after six cycles of mechlorethamine, vincristine, procarbazine, prednisone/doxorubicine, bleomycine, vinblastine treated with IF-RT had 8-year event-free survival and overall survival rates similar to those of patients in CR, suggesting a definite role for RT in these patients.

Purpose: In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy (IF-RT) without jeopardizing disease control., Patients and Methods: Patients with stage I or II HL were stratified into two groups, favorable and unfavorable, based on the following four prognostic factors: age, symptoms, number of involved areas, and mediastinal-thoracic ratio. The experimental therapy consisted of six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by IF-RT. It was randomly compared, in favorable patients, to STNI and, in unfavorable patients, to six cycles of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV hybrid) and IF-RT., Results: Median follow-up time of the 722 patients included was 9 years. In 333 favorable patients, the 10-year event-free survival rates (EFS) were 88% in the EBVP arm and 78% in the STNI arm (P = .0113), with similar 10-year overall survival (OS) rates (92% v 92%, respectively; P = .79). In 389 unfavorable patients, the 10-year EFS rate was 88% in the MOPP/ABV arm compared with 68% in the EBVP arm (P < .001), leading to 10-year OS rates of 87% and 79%, respectively (P = .0175)., Conclusion: A treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients. In favorable patients, the combination of EBVP and IF-RT can replace STNI as standard treatment. In unfavorable patients, EBVP is significantly less efficient than MOPP/ABV.

Background: To investigate the proportion, clinical characteristics and outcome of lymphocyte-rich classical Hodgkin lymphoma (LRCHL) in relation to nodular lymphocyte predominant HL (NLPHL) and classical HL (cHL)., Patients and Methods: A series of 2743 HL patients of all stages enrolled into three EORTC trials (H7, H8, H34) conducted between 1988 and 2000 and forming an unbiased series of HL patients was studied., Results: Detailed histological classification after panel review was available in 96% of the cases to allow selection of all cases with features potentially compatible with the WHO-definition of LRCHL for this study. Cases with dominance of lymphocytic infiltrate and relative paucity of eosinophils and fibrosis could be selected for re-classification. Twenty-one (0.8%) LRCHL cases were identified of which three were originally classified as NLPHL, seven as nodular sclerosis HL (NSHL) and 11 as mixed cellularity (MCHL), indicating that LRCHL is a rare disease., Conclusions: Clinical evaluation of the unselected series of patients (n = 2743) showed that LRCHL and NLPHL cases more often presented with favorable features. Clinical outcome adjusted on ab initio patient prognosis did not differ between the three histological entities. These results strongly suggest that LRCHL corresponds to an early stage in the spectrum of cHL rather than a biologically different disease entity.

The survival of patients with aggressive non-Hodgkin lymphoma (NHL) is increasing, but the incidence of secondary cancer and late toxicity is poorly defined for those treated with cyclophosphamide-hydroxydaunomycin/doxorubicin-Oncovin-prednisone (CHOP)-like chemotherapy. From February 1984 to January 1998, 2837 patients with aggressive NHL received the control-arm chemotherapy adriamycin-cyclophosphamide-vindesine-bleomycin-prednisone (ACVBP) in 3 consecutive Groupe d'Etude des Lymphomes de l'Adulte (GELA) studies. With a median follow-up time of 74 months, the 5-year overall and event-free survival rates were 60% and 52%. Two hundred two occurrences of nonneoplastic late toxicity were reported, resulting in a 5.35% cumulative probability of incidence at 7 years. Eighty-one second tumors developed, for which the 7-year cumulative incidence rate was 2.75%; 64 were solid tumors, and 17 were hematologic malignancies. In multivariate analysis, age was the only risk factor for the second development of cancer. Epidemiologic analysis allowed a comparison of this NHL group with the general population. Considering all tumors, no excess of second cancer was observed. In the male population, however, there was an excess of lung cancer (standardized incidence ratio [SIR], 2.45; P <.001) and myelodysplastic syndrome/acute myelocytic leukemia (MDS/AML) (SIR, 5.65; P =.006), and in the female population there was an excess of MDS/AML (SIR, 19.9; P <.001). With a long follow-up, the ACVBP regimen was highly effective for the treatment of aggressive NHL. Increases occurred in secondary MDS/AML and in lung cancer among men.

Our purpose was to evaluate the late physical and psychosocial difficulties of premenpausal patients treated for a localized breast cancer and to weigh the impact of chemotherapy on long-term quality of life. Two self-administered questionnaires, the EORTC core QLQ-C30 and the breast module (BR23) were mailed to 179 premenopausal node-negative women continuously disease-free, previously enrolled in a trial testing the efficacy of adjuvant CMF chemotherapy (Espié et al, 1997). The core questionnaire evaluates the physical, role, emotional, cognitive and social functioning and global health status. The breast module includes four functional scales: body image, sexual functioning, sexual enjoyment and future perspective. It also includes symptom scales such as arm or breast symptoms. Some specific professional and social states were added. 119 (68%) patients (mean age 54 years, range 30-69) participated. Mean follow-up time since diagnosis was 9.6 years (4-16). 68% had conservative and 32% radical surgery (with reconstructive surgery in 50%). CMF was given to 77 (65%) patients. Irradiation was administered in 75% of patients irrespective of adjuvant therapy. QLQ-C30 scale scores were similar in patients who had or had not received chemotherapy. Disturbance in body image, sex life and breast symptoms did not differ between patients who had or had not received adjuvant CMF. No major socioprofessional difficulties were reported except problems in borrowing from banks not related to past chemotherapy. With long follow-up, most premenopausal women treated for a localized breast cancer cope with the disease and its treatments. Adjuvant CMF chemotherapy does not appear to impair quality of life nor social and professional life in these patients., (Copyright 2000 Cancer Research Campaign.)

Purpose: To determine the prognostic factors and outcome of first-line induction failure Hodgkin's disease patients who were treated with a salvage regimen of high-dose chemotherapy and autologous stem-cell transplantation, and to compare them with matched, conventionally treated patients., Patients and Methods: We retrospectively analyzed data relating to 86 Hodgkin's disease patients who underwent autologous stem-cell transplantation after failure of the first chemotherapy regimen, either because they did not enter a complete remission and experienced progression of disease less than 3 months after the end of their first-line treatment or because they showed evidence of disease progression during first-line therapy. Graft patients were matched with 258 conventionally treated patients (three controls per case) for age, sex, clinical stage, B symptoms, and time at risk; patient data were obtained from international databases., Results: Among the 86 graft patients, the median age at diagnosis was 29 years (range, 14 to 57 years). Thirty-nine percent of patients had stage II disease, 23% had stage III disease, and 38% had stage IV disease. Seventy percent of the patients received chemotherapy and 30% received combined modality therapy; 60% of the patients received a seven- or eight-drug regimen. After this first-line treatment, 91% had disease progression and 9% had a brief partial response. Eighty patients received a second-line treatment; pretransplantation status was as follows: 24% of patients had a complete remission, 38% had a partial remission (PR), 14% had stable disease, and disease progression occurred in 24%. With a median follow-up of 22 months (range, 4 to 105 months) from diagnosis, the 5-year event-free survival and overall survival rates from transplantation were 25% and 35% (95% confidence intervals, 15 to 36 and 23 to 49), respectively. In multivariate analysis, the pretransplantation disease status after salvage therapy was the only significant prognostic factor for survival (PR: relative risk = 2.8, P = .017; progressive disease: relative risk (RR) = 5.26, P < .001). From diagnosis, the 6-year overall survival rates of the graft patients and 258 matched conventionally treated patients were 38% and 29%, respectively (P = .058)., Conclusion: Autologous stem-cell transplantation represents the best therapeutic option currently available for patients with primary induction failure and is associated with acceptable toxicity. Response to second-line treatment before high-dose chemotherapy is the only prognostic factor that can be correlated with survival.

Autologous stem-cell transplantation has become a widely used therapy in Hodgkin's disease (HD). To appreciate the early and late risks associated with this procedure, its lethal toxicity and effects on the incidence of secondary cancers were studied. Data related to 467 French patients grafted from 1982 to 1995 for primary sensitive disease (PSD, 22%), primary refractory disease (PRD, 18%), first relapse (R1, 45%), or subsequent relapses (R2, 15%) were analyzed. Grafted patients (PSD, PRD, and R1; n = 393) were matched (3 controls for 1 case) on age, gender, clinical stage, B symptoms, and time at risk with 1179 conventionally treated patients issued from international databases. The proportional hazards (Cox) model was used to assess relative risks (RR). Among grafted patients, 8% died of toxicity related to the procedure, and 18 secondary cancers occurred leading to a 5-year cumulative incidence rate of 8.9%. In this series, risk factors for second cancer were age >/=40 years (RR = 3.73, P = .007) and the use of peripheral blood stem cells as source of graft (RR = 3.10, P = .03). Among grafted and matched ungrafted patients, risk factors for the development of secondary cancer were age >/=40 years (RR = 2.90, P < .001), relapse versus no relapse (RR = 5.22, P = .006), PRD versus other patients (RR = 3.86, P = .033), and grafted versus ungrafted patients (RR = 2.04, P = . 024). Solid tumors were more frequent in grafted than in ungrafted patients (RR = 5.19, P = .001) although the incidence of myelodysplasia and acute myeloid leukemia was similar in the two groups. We conclude that high-dose chemotherapy administered as first-line treatment or after relapse is associated with an acceptable toxic death rate. The risk of secondary myelodysplasia or acute myeloid leukemia is not significantly increased after autologous stem-cell transplantation for HD, whereas an increased risk of solid tumors exists. The peripheral blood stem-cell-associated risk of secondary cancer among grafted patients needs further investigations., (Copyright 1998 by The American Society of Hematology.)

Purpose: To evaluate feasibility and efficacy of concomitant radiochemotherapy (CRCT) in Stage IIIB nonsmall-cell lung cancer (NSCLC), two induction chemotherapy cycles combining etoposide and carboplatin were first delivered, followed by CRCT with daily radiation fraction in association with carboplatin., Methods and Materials: Forty patients with biopsy-proven, locally advanced unresectable nonmetastatic NSCLC were enrolled. Induction chemotherapy consisted of two cycles (day 1 and day 28) of etoposide (VP16:100 mg/m2, days 1 to 3) and carboplatin (CBDCA:350 mg/m2, day 1). Irradiation starting at day 56, delivered 66 Gy in 2 Gy daily fraction, 5 days a week, along with a daily dose of CBDCA (15 mg/m2) given intravenously 2 to 4 h before radiation. In nonprogressive patients under induction chemotherapy, two additional cycles of VP16-CBDCA were administered 4 weeks after the completion of CRCT., Results: Out of the 40 patients enrolled (38 males, 2 females), 37 (93%) received induction chemotherapy as scheduled, with 38% Grade 3-4 hematological toxicity. Response rate to induction chemotherapy was 11% (4/37). No tumor became resectable. CRCT was delivered to 32 of these 37 patients, with full doses given to 91% of them. Clinical and hematological Grade 3-4 toxicity rates were 21 and 13%, respectively. Additional chemotherapy was delivered in 12 of 26 nonprogressive patients. At final evaluation, performed 3 months after the end of CRCT, 38% of 26 evaluable patients were responders (4 complete and 6 partial), leading to a 25% (10 of 40) overall objective response rate. Of these 10 responders, 8 became responders after CRCT only. Overall, the 1-year local control rate was 28% (11 of 40). The median survival time was 9 months and the 1-year and 2-year overall survival rates were 38 and 15%, respectively. Thirty-six patients died from local progression (25 patients), distant metastasis (9 patients), or pulmonary fibrosis (2 patients)., Conclusion: Concomitant CRCT with CBDCA is feasible with acceptable induction chemotherapy-related toxicity and a 1-year local control rate of 28%. Response rate to induction chemotherapy was low and better chemotherapy combination should be used to reduce distant failure probability and to improve local response rate before CRCT.

Background: Failure to reach complete remission (CR) with chemotherapy in advanced stages of Hodgkin's disease is considered a poor prognostic factor for progression-free and overall survival. The role of radiotherapy after chemotherapy-induced remission is controversial., Patients and Methods: In 1989, the EORTC/GPMC started a randomized phase III trial on involved-field RT (IF-RT) after MOPP/ABV hybrid-induced remission in patients with stage III/IV Hodgkin's disease. In this ongoing trial, patients in CR after chemotherapy are randomized between IF-RT and no further treatment. Patients in partial remission (PR) all receive IF-RT. Patients, age 15-70 years, with previously untreated stage III/IV Hodgkin's disease are eligible. The randomized treatment arms are still blinded. The interim analysis of May 1996 focuses on the outcome of patients in chemotherapy-induced PR., Results: A total of 405 of 493 registered patients were evaluable for response to chemotherapy. Fifty-nine percent of patients attained a CR, 37% a PR, and only 4% failed to respond. The IF-RT was actually given to 90% of the PR patients. After a median follow-up of 43 months, the five year progression-free and overall survival for patients in PR was 75% and 87%, respectively., Conclusion: IF-RT after MOPP/ABV-induced partial remission in stage III/IV Hodgkin's disease produces excellent failure-free and overall survival. Early intensification of treatment of this group of patients is not indicated.

Purpose: We report a prospective randomized study comparing the relative efficacy of alternating chemotherapy mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) with the standard MOPP chemotherapy in patients with stage IIIB and IV Hodgkin's disease (HD). The purpose is to study the influence of time of remission on clinical outcome., Patients and Methods: After two courses of MOPP, patients were randomized to receive six further courses of MOPP, or two courses of ABVD followed by two courses of MOPP and two courses of ABVD. Radiotherapy was given to areas presenting with masses > or = 5 cm and to residual masses after course no. 4. Evaluation of response (complete remission [CR]) took place after two courses (CR2), after four courses (CR4), at the end of chemotherapy (CR8), and after additional radiotherapy (CR(CT + RT)). Logistic regression analysis was used to study prognostic factors for response at the end of chemotherapy. Cox analysis was used to study prognostic factors for survival. Two hundred seven patients were registered, 192 (93%) of whom were randomized., Results: The CR rate at the end of chemotherapy (CR8) was similar in both arms (57% v 59%). However, there were more progressions in the MOPP arm compared with the MOPP/ABVD arm (23% v 8%, P = .014). A significantly higher failure-free survival (FFS) rate was found in the MOPP/ABVD arm (60% v 43% at 6 years, P = .025). There was no difference in the relapse-free survival (RFS) or survival rate. Of patients not in CR4, only 28% still reached a CR8. RFS at 6 years of patients with CR4 (69%) was not different from that of patients with CR8 (68%); patients with a CR(CT + RT)) had a lower RFS rate (48%). CR4 (P < .001) predicted strongly for final remission at the end of chemotherapy. Cox analysis showed that age more than 50 years, six or more involved lymph node areas, no CR by the fourth cycle, chemotherapy with MOPP alone, and no radiotherapy were unfavorable factors for survival., Conclusion: MOPP/ABVD chemotherapy significantly improved response and FFS rates, but had no influence on RFS and survival rates. Early CR (CR4) is an important factor for final remission and might be used to select a group of patients with a good prognosis.

Fifty-seven patients undergoing chemotherapy for osteosarcoma underwent evaluation with magnetic resonance (MR) imaging to identify changes related to a good or poor response. Spin-echo MR images obtained after preoperative chemotherapy were compared with images obtained before treatment. Histopathologic examination of each resected specimen was used to quantify the response. An increase in tumor volume and increased or unchanged edema were predictive of a poor histopathologic response (predictive values, 85%-92%). Decreased or unchanged tumor volume and a decrease in edema were poor predictors of a good response (predictive values, 56%-62%). Improved tumor demarcation, an increase in the size of areas of low signal intensity, and a decrease in joint effusion occurred independently of histopathologic response in almost half of the patients. With a subjective interpretation of MR images, poor respondents can be identified if an increase in tumor volume or no decrease in the amount of edema is seen. Subjective criteria do not contribute to the identification of good respondents.

The EORTC Lymphoma Cooperative Group and the Pierre and Marie Curie Group conducted a multicentre randomised trial on clinical stages IIIB-IV Hodgkin's disease from 1981-1986. Two hundred seven patients were registered and 192 randomised. Actuarial survival at five years for the whole group was 68%. Induction chemotherapy with eight cycles of MOPP resulted in more patients with progressive disease and fewer partial responders than a combination of MOPP and ABVD, for an equal complete remission rate. Half of the partial responders went into complete remission after radiotherapy. At five years there was no significant survival difference between the arms. Progression was recorded in 39 patients of whom only 4 survived. Relapses were most frequent in previously involved unirradiated areas. For 46 relapsed patients, including 21 early relapses within 18 months of start of treatment, the four-year survival rate was 53%. When complete remission was reached, whether early or late with combination chemotherapy or after additional radiotherapy, prognosis was independent of the way in which it was achieved. All efforts should be taken to reach a complete remission for initially progressing patients and for partial responders.

In a population of 334 patients treated for Hodgkin's disease by the European Organization for Research and Treatment of Cancer between 1964 and 1971, 21 patients with second primary cancers (SC) were observed: 4 patients with acute leukemias, 3 with non-Hodgkin's lymphomas, and 14 with solid tumors. Time to SC ranged from 2 to 16 years after initial treatment. The relative risk (RR) of acute leukemia for the patients with Hodgkin's disease as compared to the general population was 40 (P less than .001). The RR of leukemia in patients treated by polychemotherapy--mechlorethamine, vincristine, procarbazine, and prednisone--for relapse was 300 (P less than .001). However, the RR of leukemia for those patients who did not experience a relapse was 14 (not significant). The RR of other SC in the overall group was 3.76 (P less than .001). For patients whose relapses were treated by polychemotherapy the RR of SC, leukemia excepted, was 26 (P less than .001), whereas for patients not treated by polychemotherapy for relapse the RR was slightly increased (RR = 3.67; P = .027). The cumulative proportions of acute leukemia at 10 years were 0.7% in the "no-relapse" group and 2.7% in the polychemotherapy group. The cumulative proportions of other SC at 10 years was 1.3% in the no-relapse group, 7.2% in the group of patients not treated by polychemotherapy after relapse, and 8.4% in the polychemotherapy group. The first important risk factor for developing an SC was polychemotherapy, and the second was age over 40 years. These data suggest that combination chemotherapy may be responsible for both acute leukemias and other SC.

To assess the value in Ewing's sarcoma of a new multiagent therapy (vincristine, cyclophosphamide, Adriamycin, (doxorubicin) procarbazine), 30 children with a localized tumor (eight distal, nine proximal, 13 central lesions) treated at the Institut Gustave-Roussy between 1973 and 1976 (E3), were pair-matched by site of primary with 30 control patients treated without intensive chemotherapy between 1967 and 1972 (E1) at the same institution, both groups having the same local radiotherapy. Actuarial survival and disease-free survival rates at six years were significantly higher in E3 at P less than 0.01, respectively, 58% and 49% versus 25% in E1. The prognostic value of the primary site was ascertained only in children under chemotherapy. In this group there were six early relapses with death within 14 months and nine late relapses at 21 to 38 months. Among these nine patients, six died, one is living with disease, and two are currently alive in second remission. Fifteen patients are continuously free of disease 50 to 90 months after first treatment (median, 69 months): functional sequelae are minimal in six, moderate in seven, and severe in two children with limb amputation. It is concluded that in future treatments chemotherapy must be intensified and begun prior to local treatment which has to be reevaluated for radiation modalities and for radical surgery indication.

In 1980, on the basis of fundamental and clinical data, a protocol was developed at the Institut Gustave-Roussy, alternating eight monthly courses of chemotherapy (CHVP) and two or three radiotherapy sequences (15 Gy in 6 fractions of 10 days, each), to treat non-Hodgkin's lymphomas of unfavourable histologies, mainly stage II, presenting bulky tumours. Systemic, haematological and digestive tolerances were satisfactory. For 19 previously untreated stage II patients, overall survival and relapse-free survival after 30 months were 85 and 65%, respectively. Three of the relapses were observed in patients who did not receive the alternating schedule in an optimal way; this suggests that these results can be further improved.