Persistent improved results after adding vincristine and bleomycin to a cyclophosphamide/hydroxorubicin/Vm-26/prednisone combination (CHVmP) in stage III-IV intermediate- and high-grade non-Hodgkin's lymphoma

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Risk of second cancer after treatment of aggressive non-Hodgkin's lymphoma; an EORTC cohort study

Background and Objectives. Second cancer has been associated with the treatment of non-Hodgkin's lymphoma (NHL), but few studies have addressed this issue considering specific treatments.Design and Methods. We estimated risk by standardized incidence ratios (SIR) and absolute excess risk (AER) based on general population rates (European Network of Cancer Registries) in 748 patients (aged 15-82 years) treated for aggressive NHL in four successive EORTC (European Organization for Research on Treatment of Cancer) trials.Results. All patients received fully-dosed CHOP-like chemotherapy, 65% received involved-field radiotherapy and 14% high-dose treatment. Half of the patients needed salvage treatment and 37% were followed for more than 10 years. The cause of death was NHL in 79% of the patients; 4% died of second cancer with a median survival 8.9 (0.8-20.5) years. Cumulative incidences (death from any cause being a competing event) were 5% and 11% for solid cancer and 1% and 3% for acute myeloid leukemia/myelodysplastic syndrome at 10 and 15 years, respectively. Cancer risk appeared age-related: in young patients high risks were observed for leukemia (SIR 16.7, 95% Cl 1.4-93.1, AER 5.0), Hodgkin's lymphoma (SIR 60.1, 95% Cl 12.4-175.2, AER 15.7), colorectal cancer (SIR 12.5, 95% Cl 2.6-36.5, AER 14.7) and lung cancer (SIR 15.4; 95% Cl 4.2-39.4, AER 19.8), while risk in patients older than 45 years matched that in the normal population. The risk of cancer was significantly raised by smoking and salvage treatment.Interpretation and Conclusions. Half of the patients die of aggressive NHL before living long enough to experience second cancer. Only young patients have a high risk of second cancer during follow-up beyond 10 years.</p

Risk of second cancer after treatment of aggressive non-Hodgkin's lymphoma; an EORTC cohort study

Background and Objectives. Second cancer has been associated with the treatment of non-Hodgkin's lymphoma (NHL), but few studies have addressed this issue considering specific treatments. Design and Methods. We estimated risk by standardized incidence ratios (SIR) and absolute excess risk (AER) based on general population rates (European Network of Cancer Registries) in 748 patients (aged 15-82 years) treated for aggressive NHL in four successive EORTC (European Organization for Research on Treatment of Cancer) trials. Results. All patients received fully-dosed CHOP-like chemotherapy, 65% received involved-field radiotherapy and 14% high-dose treatment. Half of the patients needed salvage treatment and 37% were followed for more than 10 years. The cause of death was NHL in 79% of the patients; 4% died of second cancer with a median survival 8.9 (0.8-20.5) years. Cumulative incidences (death from any cause being a competing event) were 5% and 11% for solid cancer and 1% and 3% for acute myeloid leukemia/myelodysplastic syndrome at 10 and 15 years, respectively. Cancer risk appeared age-related: in young patients high risks were observed for leukemia (SIR 16.7, 95% Cl 1.4-93.1, AER 5.0), Hodgkin's lymphoma (SIR 60.1, 95% Cl 12.4-175.2, AER 15.7), colorectal cancer (SIR 12.5, 95% Cl 2.6-36.5, AER 14.7) and lung cancer (SIR 15.4; 95% Cl 4.2-39.4, AER 19.8), while risk in patients older than 45 years matched that in the normal population. The risk of cancer was significantly raised by smoking and salvage treatment. Interpretation and Conclusions. Half of the patients die of aggressive NHL before living long enough to experience second cancer. Only young patients have a high risk of second cancer during follow-up beyond 10 years

Late non-neoplastic events in patients with aggressive non-Hodgkin's lymphoma in four randomized European Organisation for Research and Treatment of Cancer trials.

BACKGROUND: A significant proportion of patients with aggressive non-Hodgkin's lymphoma (NHL) become long-term survivors. A European Organisation for Research and Treatment of Cancer database of patients with aggressive NHL, consistently treated with doxorubicin-based chemotherapy since 1980, afforded the possibility to explore late complications in this patient group. PATIENTS AND METHODS: Of 951 randomized patients, complete data on late complications could be collected in 757 patients who were alive > or = 2 years after the start of therapy and were seen at yearly follow-ups (median follow-up, 9.4 years; range, 2.1-20.4 years). We computed cumulative incidences of late events in a competing risk model by Gray (death being the competing event) to avoid bias caused by the high percentage of NHL-related deaths. Risk factors were estimated in a Cox proportional-hazards model and also evaluated with the Gray test. RESULTS: Late non-neoplastic events were found in 46% of the 757 patients. At 15 years, the cumulative incidences of cardiac disease and infertility were 20% and 29%, respectively. Renal insufficiency (11%), acquired hypertension (8%), and disabling neuropathy (13%) were also frequent. Salvage treatment was a risk factor in most cases. Smoking, age > 50 years during treatment, and preexistent hypertension were the main risk factors for cardiovascular disease. In-field radiation therapy (RT) was related to hypothyroidism, lung fibrosis, hypertension, gastrointestinal toxicity, and renal insufficiency but not to cardiovascular events. Autologous stem cell transplantation and cisplatin- and MOPP (mechlorethamine/vincristine/procarbazine/prednisone)-containing therapies were associated with infertility and renal insufficiency. CONCLUSION: Altogether, almost half the patients with aggressive NHL experienced events addressed as late non-neoplastic complications. Salvage therapy, smoking, age > 50 years, and in-field RT are important risk factors.Journal ArticleMulticenter StudyRandomized Controlled TrialResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Impact of involved field radiotherapy in partial response after doxorubicin-based chemotherapy for advanced aggressive non-Hodgkin's lymphoma

Purpose: Whether salvage therapy in patients with advanced aggressive non-Hodgkin's lymphorna (NHL) in partial remission (PR) should consist of radiotherapy or autologous stem-cell transplantation (ASCT) is debatable. We evaluated the impact of radiotherapy on outcome in PR patients treated in four successive European Organization for Research and Treatment of Cancer trials for aggressive NHL. Patients and Methods: Records of 974 patients (1980-1999) were reviewed regarding initial response, final outcome, and type and timing of salvage treatment. After 8 cycles of doxorubicin-based chemotherapy, 227 NHL patients were in PR and treated: 114 received involved field radiotherapy, 16 ASCT, 93 second-line chemotherapy, and 4 were operated. Overall survival (OS) and progression-free survival (PFS) after radiotherapy were estimated (Kaplan-Meier method) and compared with other treatments (log-rank). Impact on survival was evaluated by multivariate analysis (Cox proportional hazards model). Results: The median PFS in PR patients was 4.2 years and 48% remained progression-free at 5 years. Half of the PR patients converted to a complete remission. After conversion, survival was comparable to patients directly in complete remission. Radiotherapy resulted in better OS and PITS compared with other treatments, especially in patients with low to intermediate International Prognostic Index score, bulky disease, or nodal disease only. Correction by multivariate analysis for prognostic factors such as stage, bulky disease, and number of extranodal locations showed that radiotherapy was clearly the most significant factor affecting both OS and PFS. Conclusion: This retrospective analysis demonstrates that radiotherapy can be effective for patients in PR after fully dosed chemotherapy; assessment in a randomized trial (radiotherapy vs. ASCT) is justified. (c) 2006 Elsevier Inc

Erythrocyte sedimentation rate as predictive factor for early relapse and survival in 772 EORTC patients with early stage Hodgkin disease

Objective: To assess the value of an elevated (> 30 mm/h) Westergren erythrocyte sedimentation rate (ESR) for predicting early relapse and survival after therapy in patients with clinical stage I or II Hodgkin disease. Interventions: We studied 772 patients with early-stage Hodgkin disease who had participated in two separate multicenter clinical trials. Both trials used modern field radiotherapy and, in some patients, multi-agent chemotherapy. Main Results: The ESR patterns were based on pretherapy and post-therapy assessments: pattern 1, always normal (n = 261); pattern 2, elevated before therapy but normal immediately after therapy (n = 121); pattern 3, elevated before therapy but normal within 3 months after therapy (n = 89); pattern 4, always elevated (n = 48); pattern 5, normal before therapy but oscillating between normal and elevated after therapy (n = 150); pattern 6, elevated before therapy but oscillating between normal and elevated after therapy (n = 130). By multivariate analysis, independent of whether or not patients received chemotherapy in the initial therapy protocol, ESR patterns 4, 5, and 6 were shown to be the best predictors for early relapse and survival when patients were stratified according to the type of chemotherapy received and the number of involved nodal areas. Patients with ESR pattern 4 had a relative risk for death seven times that of patients with patterns 1, 2, or 3. Early relapse was the second most important factor predicting death, irrespective of ESR; patients with early relapse and ESR patterns 1, 2, or 3 had a relative risk for death of 4.5, and those with early relapse and ESR patterns 4, 5, or 6 had a relative risk for death of 15. Whether or not chemotherapy was given initially did not change the relative risk, which shows that ESR, not initial therapy, was the predictor for early relapse and death due to Hodgkin disease. Conclusion: An unexplained elevated ESR after therapy, especially after modern radiotherapy, independent of other factors, strongly suggests the presence of aggressive and resistant Hodgkin disease. An elevated ESR is predictive of early relapse and poor prognosis; its presence justifies early aggressive therapy.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Causes of death after therapy for early stage Hodgkin's disease entered on EORTC protocols

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Quality control of involved-field radiotherapy in patients with advanced Hodgkin's lymphoma (EORTC 20884)

PURPOSE: To evaluate the impact of the quality of involved-field radiotherapy (IFRT) on clinical outcome in patients with advanced Hodgkin's lymphoma (HL) in complete remission (CR) after six to eight cycles of mechlorethamine, vincristine, procarbazine, prednisone-doxorubicin, bleomycin, and vinblastine (MOPP-ABV) chemotherapy. METHODS AND MATERIALS: A retrospective review of clinical and radiologic data, radiation charts, simulator films, and megavoltage (MV) photographs was performed. IFRT consisted of 24 Gy to all initially involved nodal areas and 16-24 Gy to all initially involved extranodal sites. Major violations were defined as no or only partial irradiation of an originally involved area, or a total dose <90% of the prescribed dose. RESULTS: Of the 739 patients who were enrolled in the trial between 1989 and 2000, 57% achieved a CR; 152 of 172 patients randomized to IFRT actually received radiotherapy; and in 135 patients, quality control was performed. The overall major violation rate was 47%, predominantly concerning target volumes. The total dose was correct in 81% of the patients. After a median follow-up of 6.5 years, there was no difference in cumulative failure rate between patients with or without major violations. There was no relationship between incidence or site of relapse and major protocol violations. CONCLUSION: In advanced-stage HL patients in complete remission after six to eight cycles of MOPP-ABV, the outcome was not influenced by violation of the radiotherapy protocol