Juan C. Gutierrez

Should soft tissue sarcomas be treated at high-volume centers? An analysis of 4205 patients

Objective:To define the prognostic significance of surgical center case volume on outcome for soft tissue sarcoma (STS). Methods:STS cases registered in the Florida Cancer Data System (FCDS) between 1981 and 2001 were analyzed. Medical facilities were ranked by STS operative volume. Facilities above the 67th percentile for volume were defined as high-volume centers (HVCs). Results:Of the 4205 operative cases of STS identified, 68.1% were treated at low-volume centers (LVCs) and 31.9% at HVCs. A larger proportion of high-grade tumors (53.8% vs. 44.3%) and lesions over 10 cm (40.7% vs. 28.7%) were resected at HVC (P < 0.001). The 30-day mortality was 0.7% for HVC and 1.5% for LVC (P = 0.028), and mortality rates at 90 days were 1.6% and 3.6%, respectively (P = 0.001). Median survival was 40 months at HVC and 37 months at LVC (P = 0.002). Univariate analysis demonstrated significantly improved survival at HVC for high-grade tumors (median 30 months vs. 24 months, P = 0.001), lesions over 10 cm (28 months vs. 19 months, P = 0.001) and truncal or retroperitoneal sarcomas (39 months vs. 31 months, P = 0.011). Limb amputation rate was lower (9.4% vs. 13.8%, P = 0.048) and radiation and chemotherapy were more frequently administered at HVC (OR = 1.54). On multivariate analysis, treatment at a HVC was a significant independent predictor of improved survival (OR = 1.292, P = 0.047). Conclusions:STS patients treated at HVC have significantly better survival and functional outcomes. Patients with either large (>10 cm), high-grade or truncal/retroperitoneal tumors should be treated exclusively at a high-volume center.

Chondrosarcoma in the United States (1973 to 2003): An Analysis of 2890 Cases from the Seer Database

BACKGROUND Current demographic, prognostic, and outcomes data on the diagnosis and treatment of chondrosarcoma have been based on case series reported by individual treatment centers. The SEER (Surveillance, Epidemiology and End Results) database is a validated national epidemiological surveillance system and cancer registry that has been used extensively to evaluate treatment outcomes in cases of malignancy. The purpose of the present study was to use this database to identify demographic and prognostic characteristics of chondrosarcoma and to describe the natural history following the treatment of this rare disease in the United States over the last thirty years. METHODS Two thousand eight hundred and ninety patients with chondrosarcoma were identified in the SEER database, and information regarding the demographic and clinical characteristics of the patients, the histological features and grade of the tumors, the location and size of the tumors, the surgical stage at the time of diagnosis, the use of surgery and radiation treatment, and survival were extracted. RESULTS Comparison of the overall and disease-specific survival rates revealed that patients who survived for ten years were more likely to die of events that were unrelated to chondrosarcoma. The disease-specific survival rate leveled off at ten years of follow-up. Univariate analysis revealed that female sex, a low histological grade, and local surgical stage were associated with a significant disease-specific survival benefit. An age of fifty years or less and an appendicular location of the tumor were associated with a significant overall survival benefit. On multivariate analysis, only grade and stage had significant association with disease-specific survival. On the basis of a comparison of survival rates according to the decade of diagnosis, it appears that there has been no significant improvement in survival over the last thirty years. CONCLUSIONS Only grade and stage are independent prognostic factors for survival in cases of chondrosarcoma. Current treatment algorithms have not improved the survival rates of patients with chondrosarcoma over the past thirty years. Routine patient surveillance following treatment should be extended to ten years of follow-up.

African American and Poor Patients Have a Dramatically Worse Prognosis for Head and Neck Cancer : An Examination of 20,915 Patients

Differences in cancer survival based on race, ethnicity, and socioeconomic status (SES) are a major issue. To identify points of intervention and improve survival, the authors sought to determine the impact of race, ethnicity, and socioeconomic status for patients with cancers of the head and neck (HN).

Malignant pancreatic tumors: incidence and outcome in 58 pediatric patients.

OBJECTIVE The purpose of the study was to examine current incidence trends and outcomes for children with pancreatic malignancies. METHODS The Surveillance, Epidemiology, and End Results registry (1973-2004) was examined for pediatric patients with pancreatic malignancies (up to 19 years of age). RESULTS Malignant pancreatic neoplasms were identified in 58 patients. Females outnumbered males 1.9 to 1 (38 vs 20) for an age population-adjusted incidence of 0.021 and 0.015 per 100,000. Overall, 70% (n = 41) of patients were white. Asians had the highest incidence. Tumors were classified as exocrine (n = 31, 53.4%), endocrine (n = 19, 32.8%), or sarcomas (n = 5, 8.6%). Exocrine tumors included pancreatoblastoma (n = 10), solid-cystic tumor (SCT) (n = 10), ductal adenocarcinoma (DA) (n = 7), and acinar cell carcinoma (ACC) (n = 4). All SCTs and 80% of pancreatoblastomas were seen in females, whereas males had a higher incidence of DA 71% (P = .036). Ductal adenocarcinoma, SCT, acinar cell carcinoma, sarcomas, and endocrine tumors were more common in children older than 10 years, whereas pancreatoblastoma was more common in younger children (P = .045). Almost half of patients (n = 25) presented with distant metastasis; of these, 44% were endocrine tumors. Survival was significantly greater for female patients (P = .004) and for those who had surgery (P = .001) by both univariate and multivariate analysis. There was a significant difference in tumor type 15-year survival with DA having the worst (23%) and SCT the best (100%). CONCLUSIONS Pediatric pancreatic neoplasms are uncommon and carry a variable prognosis. Both female sex and surgery were independent predictors of improved survival.

Malignant breast cancer in children: a review of 75 patients.

OBJECTIVE To determine incidence trends and outcomes for pediatric patients with malignant breast disease. METHODS The Surveillance, Epidemiology, and End Results registry was examined for all females 19 years of age and younger diagnosed with a malignant breast tumor between 1973 and 2004. RESULTS A total of 75 patients with malignant breast tumors were identified. Overall, 14.5% of patients had in situ tumors, and 85.5% had invasive disease. Tumors were classified as being either carcinomas (n = 41, 54.7%) or sarcomas (n = 34, 45.3%). The majority of sarcomatous lesions were phyllodes tumors (n = 29, 85.5%), whereas most carcinomas were of a ductal etiology (n = 19, 46.3%). The age-adjusted incidence of all malignant pediatric breast tumors in 2003 was 0.08 cases per 100,000 people (0.03 carcinoma and 0.06 sarcoma cases per 100,000 people). In the carcinoma group, regionally advanced disease was present in 11 patients (26.8%), whereas only 3 patients (7.3%) presented with metastatic disease. All patients with sarcomatous tumors presented with localized disease. Adjuvant radiation therapy was administered in only 9.8% of carcinomas and 8.8% of sarcomas, and 85.4% of carcinoma patients and 97.1% of sarcoma patients underwent surgical resection for their primary disease. Subgroup analysis revealed 5- and 10-year survival rates of 89.6% for patients with sarcomatous tumors and 63.1% and 54.3% for carcinomas. CONCLUSIONS Malignant pediatric breast malignancies remain relatively rare. The two most common histologies of breast neoplasms in children are malignant carcinomas followed by sarcomas. Although uncommon, malignant disease must be considered in the differential diagnosis of the pediatric patient with a breast mass.

Body surface area prediction in normal, hypermuscular, and obese mice.

BACKGROUND Accurate determination of body surface area (BSA) in experimental animals is essential for modeling effects of burn injury or drug metabolism. Two-dimensional surface area is related to three-dimensional body volume, which in turn can be estimated from body mass. The Meeh equation relates body surface area to the two-thirds power of body mass, through a constant, k, which must be determined empirically by species and size. We found older values of k overestimated BSA in certain mice; thus we determined empirically k for various strains of normal, obese, and hypermuscular mice. MATERIALS AND METHODS BSA was computed from digitally scanned pelts and nonlinear regression analysis was used to determine the best-fit k. RESULTS The empirically determined k for C57BL/6J mice of 9.82 was not significantly different from other inbred and outbred mouse strains of normal body composition. However, mean k of the nearly spheroid, obese lepr(db/db) mice (k = 8.29) was significantly lower than for normals, as were values for dumbbell-shaped, hypermuscular mice with either targeted deletion of the myostatin gene (Mstn) (k = 8.48) or with skeletal muscle specific expression of a dominant negative myostatin receptor (Acvr2b) (k = 8.80). CONCLUSIONS Hypermuscular and obese mice differ substantially from normals in shape and density, resulting in considerably altered k values. This suggests Meeh constants should be determined empirically for animals of altered body composition. Use of these new, improved Meeh constants will allow greater accuracy in experimental models of burn injury and pharmacokinetics.

Loss of GDF-15 abolishes Sulindac chemoprevention in the ApcMin/+ mouse model of intestinal cancer

BackgroundGrowth-differentiation factor (GDF)-15, a member of the TGF-beta superfamily, is potently induced in the intestine following mechanical injury, genotoxic insult and following non-steroidal anti-inflammatory drugs (NSAIDs) exposure. GDF-15 expression correlates with apoptosis in intestinal cells and has been implicated in the pathogenesis of colorectal cancer formation and the anti-tumor effects of NSAIDs. We sought to determine the effect of loss of Gdf15 on animal tumor models of hereditary colon cancer and in the NSAID-mediated prevention of heritable colorectal cancer.MethodsGDF-15 null (Gdf15−/−) mice and mice with the genetic mutation found in hereditary poliposis coli, Apcmin/+ were bred. Gdf15−/−, Apcmin/+ and Gdf15+/+, Apcmin/+ mice were generated.ResultsIn Gdf15−/−, Apcmin/+ mice, intestinal neoplasia formation rate and size were indistinguishable from that in Gdf15+/+, Apcmin/+ mice. Sulindac chemoprotection activity although potent in Gdf15+/+, Apcmin/+ mice was abolished in Gdf15−/−, Apcmin/+ mice.ConclusionsThese results demonstrate in a murine model that GDF-15 does not significantly regulate heritable in vivo intestinal carcinogenesis but does mediate sulindac chemoprevention in heritable colon cancer. These data suggest that the use of GDF-15 activated signaling pathways may allow improved chemoprevention and therapies for colorectal cancer.

Are many community hospitals undertreating breast cancer?: lessons from 24,834 patients.

Objective:To compare treatment patterns and long-term outcomes between teaching and community hospitals treating patients with infiltrating ductal carcinoma (IDC). Methods:All IDCs from the Florida Cancer Data System from 1994 to 2000 were examined. Results:Overall, 24,834 operative cases of IDC were identified. Teaching hospitals treated 11.3% of patients with a larger proportion of stage III and IV disease (39.8% vs. 33.0%). Five- and 10-year overall survival rates at teaching hospitals were 84% and 72%, compared with 81% and 69% at high-volume community hospitals and 77% and 63% at low-volume hospitals (P < 0.001). The greatest differences on survival were observed in patients with advanced IDC. Examination of practice patterns demonstrated that multimodality therapy was most frequently administered in teaching hospitals. Breast-conserving surgery was more frequently performed at teaching hospitals (41.5% vs. 38.9% P = 0.008). On multivariate analysis, it was found that treatment at a teaching hospital was a significant independent predictor of improved survival (hazard ratio = 0.763, P < 0.001). This survival benefit was greater and independent of high-volume center status (hazard ratio = 0.903, P < 0.02). Conclusions:Patients with IDC treated at teaching hospitals have significantly better survival than those treated at high-volume centers or community hospitals, particularly in the setting of advanced disease. Poorer long-term outcomes for IDC at community hospitals seem to be, at least in part, because of decreased use of proven life-extending adjuvant therapies. These results should encourage community hospitals to institute changes in treatment approaches to invasive breast cancer to optimize patient outcomes.

Does Children's Oncology Group hospital membership improve survival for patients with neuroblastoma or Wilms tumor?

To determine prognostic significance of hospital surgical volume and Childrens Oncology Group (COG) membership on neuroblastoma (NBL) and Wilms tumor (WT) survival.

Cancer care in the pediatric surgical patient: A paradigm to abolish volume-outcome disparities in surgery

BACKGROUND The objective of this study was to define the prognostic significance of hospital surgical volume on outcomes for pediatric neuroblastoma and Wilms tumor. METHODS The Florida Cancer Data System was examined for all pediatric patients treated between 1981 and 2004. RESULTS Of the 869 patients with neuroblastoma identified, 463 were treated at 5 high-volume centers (HVC) and 406 were treated at 61 low-volume centers (LVC). There were no differences in sex, age at diagnosis, race, ethnicity, or stage of disease between the 2 groups. The 5- and 10-year survival rates were identical between treatment groups (70.6% and 67.7% at HVC vs 69.3% and 65.2% at LVC, P = .243). Multivariate analysis identified age at diagnosis and tumor stage as independent prognostic factors. Of the 790 patients with Wilms tumor identified, 395 were treated at 5 HVC and 395 were treated at 50 LVC. There were no differences in sex, age of diagnosis, or stage of disease between the 2 groups. The 5- and 10-year survival rates were identical between treatment groups (91.3% and 89.9% at HVC vs 89.7% and 88.5% at LVC, P = .698). Multivariate analysis identified ethnicity, tumor stage, and use of chemotherapy as independent prognostic factors. CONCLUSION Survival rates for patients with neuroblastoma and Wilms tumor are unrelated to the hospital surgical volume or patient race. This result stands in stark contrast to a variety of adult malignancies. Models used for pediatric patient care for cancer may provide insight into ways to improve the treatment of adult patients in need of complex cancer care.