Therapeutic radiation for lymphoma: risk of malignant mesothelioma

BACKGROUND: Ionizing radiation has been used since the 1950s to treat a variety of cancers. Cancer patients who are treated with radiotherapy have shown increased risks for a variety of second malignancies, including mesothelioma, in several recent reports. The only existing study of Hodgkin lymphoma (HL) and subsequent mesothelioma had a short observation period. METHODS: The authors used Surveillance, Epidemiology, and End Results data over a 30-year period to identify patients with HL and non-Hodgkin lymphoma (NHL) who also were diagnosed with mesothelioma. Standardized incidence ratios (SIR) and absolute excess risks were calculated by sex and treatment modality for both types of lymphoma. RESULTS: Twenty-six patients were identified who had mesothelioma as second primaries based on 21,881 diagnoses of HL and 101,001 diagnoses of NHL. There was a statistically significant increase in mesothelioma (4 diagnoses; SIR, 6.59; 95% confidence interval [95% CI], 1.79-16.87) among men with HL who received radiation, but no women survivors were identified who had a diagnosis of mesothelioma. For NHL survivors, there was a nonsignificant excess of mesothelioma among men (SIR, 1.91; 95% CI, 0.77-3.93) and women (SIR, 3.75; 95% CI, 0.77-10.95) who had received radiation treatment. There were no increases among patients who were unirradiated. CONCLUSIONS: Mesothelioma rates for patients who had received radiotherapy were increased for survivors of HL and NHL. No increases were observed among the unirradiated. These findings and the existing body of supporting studies confirmed that radiotherapy is a cause of mesothelioma.     

Radiation therapy is associated with improved survival in patients with pancreatic adenocarcinoma: results of a study from the Surveillance, Epidemiology, and End Results (SEER) registry data

BACKGROUND: The role of adjuvant radiation therapy in pancreatic cancer is controversial. For the current study, the authors evaluated the effect of preoperative and postoperative radiation therapy on survival in patients with pancreatic adenocarcinoma. METHODS: The analysis included 3008 patients who were reported to the Surveillance, Epidemiology, and End Results registry of the National Cancer Institute from 1988 to 2002 who had adenocarcinoma of the pancreas and who underwent cancer-directed surgery. A retrospective analysis of overall survival and cancer-specific survival for these patients was performed using the Kaplan-Meier method. Comparative risks of mortality were evaluated by using multivariate-adjusted Cox regression models. RESULTS: Of 3008 patients, 1267 (42%) received radiation therapy. Overall survival improved significantly in patients who received radiation therapy, with a median survival of 17 months and a 5-year overall survival rate of 13% in patients who received radiation compared with 12 months and 9.7%, respectively, for patients who did not receive radiation therapy (P < .0001). On multivariate analysis, radiation therapy was associated with improvement in overall survival in patients who had direct extension beyond the pancreas and/or regional lymph node involvement (P < .01) but not in patients with T1-T2N0M0 disease (P > .05). Radiation therapy was associated with improvement in cause-specific survival in patients who had regional lymph node involvement (P < .02) but not in patients who had T1-2N0M0 disease or direct extension beyond the pancreas without lymph node involvement (P > .05). Differences in overall and cause-specific survival among patients who received preoperative versus postoperative radiation therapy did not reach statistical significance. CONCLUSIONS: Radiation therapy was associated with improved survival compared with cancer-directed surgery without radiation in patients with adenocarcinoma of the pancreas.     

A Surveillance, Epidemiology, and End Results analysis of small cell carcinoma of the bladder: epidemiology, prognostic variables, and treatment trends

BACKGROUND:

Small cell carcinoma of the urinary bladder (SCCB) is difficult to characterize and study because of its rarity. For the current study, a large population‐based database was used to address ill‐defined clinical parameters for this disease.

METHODS:

The authors analyzed the incidence, sociodemographics, prognostic variables, and treatment trends of this cancer in the Surveillance, Epidemiology, and End Results (SEER) limited database (1991‐2005). The SEER‐Medicare database (1991‐2005) was used to estimate chemotherapy use.

RESULTS:

There were 642 patients in the SEER limited dataset. From 1991 to 2005, the incidence of SCCB increased significantly from 0.05 to 0.14 cases per 100,000 population (P < .01; approximately 500 new cases of SCCB per year, representing 0.7% of all bladder malignancies). The median overall survival was 11 months. Elderly Caucasian men were the most commonly affected (ratio of Caucasians to non‐Caucasians, 10:1; ratio of men to women, 3:1; median age, 73 years). Age, race, marital status, and TNM staging were identified as independent prognostic variables (P < .05). Patients who had stage IV disease without distant metastasis (ie, positive lymph node status) had overall and cancer‐specific survival rates similar to those of patients who had stage I through III disease, but they had significantly better survival compared with patients who had distant metastasis (P < .0001). Transurethral resection of the bladder tumor became the most common surgical treatment (P < .0001), representing 55% of patients from 2001 to 2005. The receipt of radiation and chemotherapy did not change significantly during the study period.

CONCLUSIONS:

These comprehensive data delineated the patient population for this rare disease, described several independent prognostic variables, and demonstrated clear treatment trends for this disease. The results suggest that a simpler staging system (ie, limited stage vs extensive stage) may be appropriate for patients with SCCB. Cancer 2011;. © 2011 American Cancer Society.     

Conditional probability of long‐term survival in glioblastoma

BACKGROUND:

Advances in glioblastoma care have resulted in a larger proportion of patients surviving beyond 2 years after diagnosis. It is not clear how long‐term survivors should be counseled with respect to future prognosis, or what factors influence that prognosis. The conditional probability of survival was evaluated from multiple time points in patients with glioblastoma, using Surveillance, Epidemiology, and End Results (SEER) data.

METHODS:

Patients diagnosed with glioblastoma from 1998 to 2008 who were treated with radiation‐containing regimens were identified within SEER data. Conditional survival probabilities from multiple survival points were calculated. Cox proportional hazards models were constructed to identify predictors of survival from diagnosis and from 1 and 2 years after diagnosis.

RESULTS:

A total of 10,022 patients with glioblastoma met study inclusion criteria; median survival was 12.61 months. Conditional probability of surviving an additional 2 years ranged from 19.8% at diagnosis to 65.9% at 5 years after diagnosis. The proportion of patients surviving 12 months from time of diagnosis as well as from 6, 12, and 18 months after diagnosis was significantly higher in patients diagnosed in 2005 through 2008 than those diagnosed in 1998 through 2004. Of demographic and treatment‐related factors evaluated, only age was associated with hazard of death at diagnosis and 1 and 3 years after diagnosis (P < .0001 at each time point).

CONCLUSIONS:

Patients surviving past 2 years from diagnosis have a relatively favorable conditional probability of survival into the future compared to newly diagnosed patients. This effect becomes more pronounced with increasing time since diagnosis. These data will assist in the counseling of glioblastoma survivors. Cancer 2012. © 2012 American Cancer Society.     

Differential expression of cell adhesion genes: implications for drug resistance

It is well known that tumors arising from tissues such as kidney, pancreas, liver and stomach are particularly refractory to treatment. Searching for new anticancer drugs using cells in culture has yielded some effective therapies, but these refractory tumors remain intractable. Studies that compare cells grown in suspension to similar cells grown attached to one another as aggregates have suggested that it is adhesion to the extracellular matrix of the basal membrane that confers resistance to apoptosis and, hence, resistance to cytotoxins. The genes whose expression correlates with poor survival might, therefore, act through such a matrix-to-cell suppression of apoptosis. Indeed, correlative mining of gene expression and patient survival databases suggests that poor survival in patients with metastatic cancer correlates highly with tumor expression of a common theme: the genes involved in cell adhesion and the cytoskeleton. If the proteins involved in tethering cells to the extracellular matrix are important in conferring drug resistance, it may be possible to improve chemotherapy by designing drugs that target these proteins.     

A comparison of the demographics, clinical features, and survival of patients with adenoid cystic carcinoma of major and minor salivary glands versus less common sites within the Surveillance, Epidemiology, and End Results registry

BACKGROUND:

The scientific literature to date lacks population‐based studies on the demographics, clinical features, and survival of patients with adenoid cystic carcinoma (ACC) of different anatomic sites.

METHODS:

The authors identified 5349 patients who had ACC of the major salivary glands (N = 1850), minor salivary glands (N = 2077), breast (N = 696), skin (N = 291), lung and bronchus (N = 203), female genital system (N = 132), and eye and orbit (N = 100) from the Surveillance, Epidemiology, and End Results (SEER) registry. Differences in demographics, clinical features, and survival of patients were assessed.

RESULTS:

ACC of the eye and orbit was associated with younger age at presentation (mean age,49.9 years). ACC of the skin or breast tended to present with less aggressive prognostic features, whereas ACC of the lung and bronchus or eye and orbit tended to present with more aggressive prognostic features. In a multivariate survival analysis of patients who presented with localized disease, patients with ACC of the breast (hazard ratio [HR], 0.40) or skin (HR, 0.40) had a significantly lower risk death than patients with ACC of the major salivary glands; whereas patients with ACC of the lung and bronchus (HR, 3.72) or the eye and orbit (HR, 3.67) had a significantly higher risk. For patients who presented with regional disease, the only clear prognostic difference in multivariate analysis was that patients with ACC of skin fared significantly better.

CONCLUSIONS:

The demographics and clinical features of patients with ACC differ by disease site. The current results indicated that site may be an important predictor of survival for patients who present with localized disease but is less important for patients who present with regional disease. Cancer 2012. © 2011 American Cancer Society.     

Understanding bladder cancer death

BACKGROUND:

To the authors' knowledge, the extent to which death from bladder cancer is attributable to tumor biology or physician practice patterns is unknown. For this reason, the relative importance of broadening indications for aggressive therapy has unclear implications.

METHODS:

Patients whose deaths were caused directly by bladder cancer were identified using institutional (n = 126 patients) and administrative (n = 6326 patients) data sources. By using implicit review (clinical data, 2001‐2005) and explicit algorithms (Surveillance, Epidemiology, and End Results [SEER]‐Medicare, 1992‐2002), the authors estimated the proportion of potentially avoidable deaths from bladder cancer.

RESULTS:

After an implicit review of clinical data, 40 of 126 deaths (31.7%) were classified as potentially avoidable. Compared with those patients who were deemed unsalvageable, these patients generally presented with nonmuscle‐invasive disease (80% vs 25.6%; P < .001), received multiple courses of intravesical therapy (32.5% vs 1.2%; P < .001), and had a more protracted course from diagnosis to aggressive treatment (median, 23 months vs 2 months; P < .001). An explicit review of claims data indicated that between 31.6% and 46.8% of the 6326 bladder cancer deaths identified in the SEER‐Medicare data potentially were avoidable, depending on the survivorship threshold chosen. Patients whose deaths potentially were avoidable more commonly presented with nonmuscle‐invasive disease (66.7% vs 24.7%; P < .0001) and lower grade disease (35.1% vs 15.1%; P < .0001).

CONCLUSIONS:

The greatest inroads into reducing death from bladder cancer likely hinge on earlier detection or improvement of systemic therapies. However, changing physician practice may translate into nontrivial reductions in bladder cancer mortality. Cancer 2009. © 2009 American Cancer Society.     

Improved survival with adjuvant external-beam radiation therapy in lymph node-negative pancreatic cancer: a United States population-based assessment

BACKGROUND: Although chemoradiation often is administered as an adjuvant to pancreatic cancer surgery, recent reports have disputed the benefit of radiation therapy. The objective of this study was to determine the effect of adjuvant radiation therapy in patients with locally confined, lymph node-negative (N0) pancreatic cancer. METHODS: The Surveillance, Epidemiology, and End Results registry was used to identify patients who had undergone cancer-directed surgery for N0 pancreatic adenocarcinoma between 1988 and 2003. Kaplan-Meier survival curves were constructed to compare overall survival between patients who did and did not receive adjuvant external-beam radiation therapy (EBRT). Multivariate Cox regression analysis was used to determine the prognostic significance of EBRT when additional clinicopathologic factors were assessed. The analysis also examined the potential treatment selection bias of patients with survival <3 months. RESULTS: A cohort of 1930 surgical patients with N0 disease was identified. The median survival was 17 months. Irradiated patients had significantly better survival compared with nonirradiated patients (20 months vs 15 months, respectively; P < .001). On multivariate analysis, adjuvant EBRT (hazard ratio [HR], 0.72; 95% confidence interval [95% CI], 0.63-0.82; P < .001), age, grade, tumor classification, and tumor location were independent predictors of survival. When patients with survival <3 months were excluded from the analysis, no difference in survival between the EBRT group and the nonradiation group was noted on univariate comparison (P value not significant). However, on multivariate analysis, EBRT remained an independent predictor of improved overall survival (HR, 0.87; 95% CI, 0.75-1.00; P = .044). CONCLUSIONS: Adjuvant EBRT was associated with improved survival in patients with operable, N0 pancreatic cancer. Its use should be considered in patients who have early-stage N0 disease.