The impact of involved field radiation therapy in the treatment of relapsed or refractory non-Hodgkin lymphoma with high-dose chemotherapy followed by hematopoietic progenitor cell transplant.

BACKGROUND: Patients with refractory/relapsed non-Hodgkin lymphoma (NHL) often receive high-dose chemotherapy (HDCT) followed by hematopoietic progenitor cell transplant (HPCT) as salvage therapy. We examined the role of involved field radiation therapy (IFRT) in this setting. METHODS: The records of 167 patients with refractory/relapsed NHL who underwent HDCT followed by HPCT between February 1990 and November 2003 were reviewed. Fifty-three patients received IFRT and 114 did not receive IFRT in the peritransplant period. RESULTS: Eighty patients were alive at the time of analysis with a median follow up for alive patients of 4.5 years in the no IFRT group and 4.2 years in the IFRT group (P = 0.53). Patients undergoing IFRT were more likely to have bulky (P = 0.02) and extranodal (P= 0.04) disease at initial diagnosis. There was no significant difference between the treatment groups regarding mortality in the first 100 days after HPCT (P = 0.31). Five-year overall survival rates were 46.7% for the no IFRT group and 40.0% for the IFRT group (P= 0.15). Disease-free survival was significantly worse for patients receiving IFRT (P = 0.02); however, when considering local control, the addition of IFRT resulted in a 5-year rate similar to that for patients who did not receive IFRT (68.6% vs. 72.0% respectively, P= 0.73). CONCLUSIONS: Although disease-free survival was inferior in patients who received IFRT, despite more adverse clinical features the use of IFRT resulted in similar rates of local control and overall survival compared with those who did not receive IFRT. The use of IFRT was not associated with an increase in the risk of acute mortality or late events.

The risk of secondary malignancies over 30 years after the treatment of non-Hodgkin lymphoma.

BACKGROUND: Survivors of non-Hodgkin lymphoma (NHL) are at increased risk for developing secondary malignancies. For the current study, the authors quantitated this risk in a group of NHL survivors over 30 years of follow-up. METHODS: Standardized incidence ratios (observed-to-expected [O/E] ratio) and absolute excess risk of secondary malignancies were assessed in 77,876 patients who were diagnosed with NHL between 1973 and 2001 from centers that participated in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. RESULTS: There were 5638 patients who developed secondary malignancies, significantly more than the endemic rate (O/E, 1.14; P < .001). Overall, irradiated patients had a similar risk of secondary malignancies compared with unirradiated patients (relative risk, 1.04; 95% confidence interval, 0.98-1.10; P = .21). Irradiated patients had excess risk for sarcomas, breast cancers, and mesothelioma compared with unirradiated survivors (P < .05). Patients age <25 years at the time of their NHL diagnosis had the highest relative increased risk (no radiation: O/E, 2.1; P < .05; radiation: O/E, 4.51; P < .05). Overall, no statistical difference was observed for secondary cancer incidence between females and males (O/E, 1.12 vs. 1.15, respectively). Female survivors of NHL were less likely to develop breast cancer than the general population (O/E, 0.85; P < .05), but women age <25 years at the time of their NHL diagnosis were more likely to develop breast cancer (no radiation: O/E, 2.1; P < .05; radiation: O/E, 4.51; P < .05). CONCLUSIONS: The overall risk of secondary malignancies was increased for NHL survivors and varied according to age at NHL diagnosis, gender, and treatment.

The impact of involved field radiation therapy for patients receiving high-dose chemotherapy followed by hematopoietic progenitor cell transplant for the treatment of relapsed or refractory Hodgkin disease.

OBJECTIVES: Patients with refractory/relapsed Hodgkin disease (HD) often receive high-dose chemotherapy (HDCT) followed by hematopoietic progenitor cell transplant (HPCT) as salvage therapy. This study sought to determine if involved field radiation therapy (IFRT) in this setting improves patient outcomes. METHODS: The records of 65 patients with refractory/relapsed HD who underwent HDCT followed by HPCT between September 1988 and October 2003 were retrospectively reviewed. Forty-four patients did not receive IFRT and 21 received IFRT. RESULTS: Thirty-eight patients were alive at the time of analysis with a median follow-up of 3.4 years in the no IFRT group and 1.8 years in the IFRT group (P = 0.38). IFRT patients were more likely to have bulky disease at initial diagnosis (P = 0.05). Progression-free survival (PFS) was similar in the 2 groups (P = 0.83). Twenty-two patients in the no IFRT group and 5 in the IFRT group have died (P = 0.06). Five-year overall survival rates were 55.6% for the no IFRT group and 73.3% for the IFRT group (P = 0.16). There was no significant difference between the treatment groups regarding mortality in the first 100 days after HPCT (P = 0.41), late events (P = 0.26), or failure in sites previously involved with disease (P = 0.76). CONCLUSIONS: Although the current study did not demonstrate an improvement in PFS with the addition of IFRT to HDCT and HPCT, there was a trend toward improved overall survival. The potential benefit of IFRT may be underestimated because of the heterogeneity of the treatment groups. The use of IFRT was not associated with an increase in the risk of acute mortality or late events.

Time interval to the development of breast carcinoma after treatment for Hodgkin disease.

BACKGROUND: Women with Hodgkin disease (HD) who received mantle irradiation had an increased risk of developing breast carcinoma. The authors examined the influence of radiotherapy on the time interval to the development of breast carcinoma. METHODS: Using population, cancer incidence, and survival data from the Surveillance, Epidemiology, and End Results (SEER) registries, standardized incidence ratios (SIR) were calculated and Kaplan-Meier curves were constructed to estimate breast carcinoma-free survival in women with HD treated with and without radiotherapy. The log-rank test was utilized and multivariate proportional hazard regression analysis was performed. Multivariate analysis was also performed using the PHPH regression model. RESULTS: In 9 SEER registries, 8036 females were identified who were diagnosed with HD between 1973 and 1999. Of these women, 183 (2.3%) were subsequently diagnosed with breast carcinoma. The use of radiotherapy in the treatment of HD resulted in an increased risk of development of breast carcinoma (SIR = 1.90, P < 0.01). The log-rank test and proportional hazard regression model failed to detect a difference (P = 0.79) in breast carcinoma-free survival for women treated with and without radiotherapy. The PHPH regression model revealed that the use of radiotherapy had an adverse effect on long-term survival (relative risk [RR] = 1.84, P = 0.01), but was associated with a short-term survival advantage (RR = 0.45, P = 0.01). CONCLUSIONS: Use of the PHPH model indicated that the use of radiotherapy in the treatment of HD resulted in an increased long-term risk for the subsequent development of breast carcinoma, but conferred a short-term reduction.

Induction chemotherapy followed by radical local therapy for locally advanced non-small cell lung cancer.

Many patients who receive a diagnosis of non-small cell lung cancer (NSCLC) have locally advanced disease at initial presentation. Historically, these patients were treated with primary thoracic radiation therapy and had poor long-term survival rates, secondary to both progression of local disease and development of distant metastases. With the goal of improving clinical outcomes, multiple concepts of combined-modality therapy for locally advanced NSCLC have been investigated. The rationale for using chemotherapy in the induction regimen is to eliminate subclinical metastatic disease while improving local control. The optimal treatment of locally advanced NSCLC continues to evolve, but combined-modality therapy has led to improved survival rates compared to treatment with radiation alone and has become the new standard of care. This report reviews the major trials that have investigated various combinations of surgery, radiation therapy, and chemotherapy in the treatment of locally advanced NSCLC.