Background. Second malignancies have been associated with NonHodgkin Lymphoma treatment. Most studies report a high risk of second cancers (2 to 8 fold increase), mainly due to high ncidence of MDS/AML and solid tumors, such as lung, bladder and gastro-intestinal cancers. Nevertheless few analyses have addressed this issue focusing on indolent lymphoma. Aims. Aims of this study are to determine the incidence and the risk factors for the development of second cancers during long term follow up of patients treated for indolent lymphoma. Methods. The Gruppo Italiano Studio Linfomi (GISL) maintains a database on clinical characteristics, treatment and follow up of all patients who entered clinical trials. To address a uniform patients population inthis study, we identified 563 previously untreated patients with histologically confirmed diagnosis of indolent lymphoma, enrolled in GISL trials between 1988 and 2003. The incidence (numbers of second neoplasia by person-years under analysis) of second cancers in the study population was compared to the incidence of solid cancers in the Italian population, utilizing age-, sex- and calendar period-specific incidence rates, derived from ISTAT database. Standardized incidence ratio (SIR, the observed/expected ratio) and absolute excess risk (AER, observedcases in our cohort minus numbers expected, divided by person-years at risk) were calculated after stratifying for age cohorts. Time Free to second Tumor (TF2T) was measured from the end of the first treatment to last follow-up or date of diagnosis of second tumor. TF2T was calculated with a Kaplan-Meier estimate. Effects of potential risk factors on second cancer rates were examined in a Cox proportional-hazard model. Results. After a median follow-up of 62 months , we observed 33 cases (6%) of second cancers, including hematologic malignancies (2%). Ten out of 33 patients developed MDS/AML and 23 solid tumors, including 6 lung cancer, 6 gastro-intestinal cancer and 11 other type of cancers. Overall, incidence rate (1000 person-years) was 11.5. Excess of risk forsecond solid cancer was detected in the cohort age 50-54 (SIR =4,2; 95% CI 1.9-9.40; AER =1.27). Median TF2T was 28 months for MDS/AML, 44 for lung cancer and 47 for gastro-intestinal cancer. By univariate and Cox regression analysis, after stratifying for histology, we observed a significant negative impact (all p<.05) on TF2T for age at first treatment, male sex and fludarabine-containing therapy. Further, we divided thelog(HR), estimated by Cox regression analysis based on age, male sex and fludarabine-containing therapy, at the 33° and the 66° percentiles. Based on this analysis, we observed three groups with significant difference in the risk of developing second cancers (p<0.0001). Conclusions. Patients treated for indolent lymphoma are at elevated risk of developing second primary malignancies. The SIR and AER are increased in patients who were younger at first treatment. Age, male sex and fludarabine-containing chemotherapy have a negative impact on TF2T. Finally,utilizing these parameters in a Cox regression model, we were able to identify groups with an increased risk of second malignancies.
SECOND MALIGNANCIES AFTER TREATMENT FOR INDOLENT LYMPHOMA: A 16 YEARS FOLLOW-UP STUDY / Sacchi, Stefano; Marcheselli, Luigi; Bari, Alessia; Marcheselli, Raffaella; Pozzi, Samantha; Luminari, Stefano; M., Lombardo; G., Buda; A., Lazzaro; P., Gobbi; C., Stelitano; M., Brugiatelli. - In: HAEMATOLOGICA. - ISSN 0390-6078. - STAMPA. - 92:(2007), pp. 264-264. (Intervento presentato al convegno 12th Congress of the European Hematology Association tenutosi a VIENNA nel 7-10 GIUGNO 2007).
SECOND MALIGNANCIES AFTER TREATMENT FOR INDOLENT LYMPHOMA: A 16 YEARS FOLLOW-UP STUDY
SACCHI, Stefano;MARCHESELLI, Luigi;BARI, Alessia;MARCHESELLI, Raffaella;POZZI, Samantha;LUMINARI, Stefano;
2007
Abstract
Background. Second malignancies have been associated with NonHodgkin Lymphoma treatment. Most studies report a high risk of second cancers (2 to 8 fold increase), mainly due to high ncidence of MDS/AML and solid tumors, such as lung, bladder and gastro-intestinal cancers. Nevertheless few analyses have addressed this issue focusing on indolent lymphoma. Aims. Aims of this study are to determine the incidence and the risk factors for the development of second cancers during long term follow up of patients treated for indolent lymphoma. Methods. The Gruppo Italiano Studio Linfomi (GISL) maintains a database on clinical characteristics, treatment and follow up of all patients who entered clinical trials. To address a uniform patients population inthis study, we identified 563 previously untreated patients with histologically confirmed diagnosis of indolent lymphoma, enrolled in GISL trials between 1988 and 2003. The incidence (numbers of second neoplasia by person-years under analysis) of second cancers in the study population was compared to the incidence of solid cancers in the Italian population, utilizing age-, sex- and calendar period-specific incidence rates, derived from ISTAT database. Standardized incidence ratio (SIR, the observed/expected ratio) and absolute excess risk (AER, observedcases in our cohort minus numbers expected, divided by person-years at risk) were calculated after stratifying for age cohorts. Time Free to second Tumor (TF2T) was measured from the end of the first treatment to last follow-up or date of diagnosis of second tumor. TF2T was calculated with a Kaplan-Meier estimate. Effects of potential risk factors on second cancer rates were examined in a Cox proportional-hazard model. Results. After a median follow-up of 62 months , we observed 33 cases (6%) of second cancers, including hematologic malignancies (2%). Ten out of 33 patients developed MDS/AML and 23 solid tumors, including 6 lung cancer, 6 gastro-intestinal cancer and 11 other type of cancers. Overall, incidence rate (1000 person-years) was 11.5. Excess of risk forsecond solid cancer was detected in the cohort age 50-54 (SIR =4,2; 95% CI 1.9-9.40; AER =1.27). Median TF2T was 28 months for MDS/AML, 44 for lung cancer and 47 for gastro-intestinal cancer. By univariate and Cox regression analysis, after stratifying for histology, we observed a significant negative impact (all p<.05) on TF2T for age at first treatment, male sex and fludarabine-containing therapy. Further, we divided thelog(HR), estimated by Cox regression analysis based on age, male sex and fludarabine-containing therapy, at the 33° and the 66° percentiles. Based on this analysis, we observed three groups with significant difference in the risk of developing second cancers (p<0.0001). Conclusions. Patients treated for indolent lymphoma are at elevated risk of developing second primary malignancies. The SIR and AER are increased in patients who were younger at first treatment. Age, male sex and fludarabine-containing chemotherapy have a negative impact on TF2T. Finally,utilizing these parameters in a Cox regression model, we were able to identify groups with an increased risk of second malignancies.Pubblicazioni consigliate
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