Shifting Sociodemographic Characteristics of a Phase I Clinical Trial Population at an NCI-Designated Comprehensive Cancer Center in the Southeast.

Racial and ethnic minority populations are consistently under-represented in oncology clinical trials despite comprising a disproportionate share of a cancer burden. Phase I oncology clinical trials pose a unique challenge and opportunity for minority inclusion. Here we compared the sociodemographic characteristics of patients participating in phase 1 clinical trials a National Cancer Institute ( NCI)-designated comprehensive center to all patients at the center, patients with new cancer diagnosis in metropolitan Atlanta and patients with new cancer diagnoses in the state of Georgia. From 2015 to 2020, 2325 patients (43.4% female, 56.6% male) consented to participate in a phase I trial. Grouped self-reported race distribution was 70.3% White, 26.2% Black, and 3.5% other. Of new patient registrations at Winship Cancer Institute (N = 107 497) (50% F, 50% M), grouped race distribution was 63.3% White, 32.0% Black, and 4.7% other. Patients with new cancer diagnoses in metro Atlanta from 2015 to 2016 (N = 31101) were 58.4% White, 37.2% Black, and 4.3% other. Race and sex distribution of phase I patients was significantly different than Winship patients (P < .001). Over time, percent of White patients decreased in both phase I and Winship groups (P = .009 and P < .001, respectively); percentage of females did not change in either group (P = .54 phase I, P = .063 Winship). Although phase I patients were more likely to be White, male, and privately ensured than the Winship cohort, from 2015 to 2020 the percentage of White patients in phase I trials and among all new patients treated at Winship decreased. The intent of characterizing existing disparities is to improve the representation of patients from racial and ethnic minority backgrounds in phase I clinical trials.

Optimal Surveillance Frequency After CRS/HIPEC for Appendiceal and Colorectal Neoplasms: A Multi-institutional Analysis of the US HIPEC Collaborative.

BACKGROUND: No guidelines exist for surveillance following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal and colorectal cancer. The primary objective was to define the optimal surveillance frequency after CRS/HIPEC. METHODS: The U.S. HIPEC Collaborative database (2000-2017) was reviewed for patients who underwent a CCR0/1 CRS/HIPEC for appendiceal or colorectal cancer. Radiologic surveillance frequency was divided into two categories: low-frequency surveillance (LFS) at q6-12mos or high-frequency surveillance (HFS) at q2-4mos. Primary outcome was overall survival (OS). RESULTS: Among 975 patients, the median age was 55 year, 41% were male: 31% had non-invasive appendiceal (n = 301), 45% invasive appendiceal (n = 435), and 24% colorectal cancer (CRC; n = 239). With a median follow-up time of 25 mos, the median time to recurrence was 12 mos. Despite less surveillance, LFS patients had no decrease in median OS (non-invasive appendiceal: 106 vs. 65 mos, p < 0.01; invasive appendiceal: 120 vs. 73 mos, p = 0.02; colorectal cancer [CRC]: 35 vs. 30 mos, p = 0.8). LFS patients had lower median PCI scores compared with HFS (non-invasive appendiceal: 10 vs. 19; invasive appendiceal: 10 vs. 14; CRC: 8 vs. 11; all p < 0.01). However, on multivariable analysis, accounting for PCI score, LFS was still not associated with decreased OS for any histologic type (non-invasive appendiceal: hazard ratio [HR]: 0.28, p = 0.1; invasive appendiceal: HR: 0.73, p = 0.42; CRC: HR: 1.14, p = 0.59). When estimating annual incident cases of CRS/HIPEC at 375 for non-invasive appendiceal, 375 invasive appendiceal and 4410 colorectal, LFS compared with HFS for the initial two post-operative years would potentially save $13-19 M/year to the U.S. healthcare system. CONCLUSIONS: Low-frequency surveillance after CRS/HIPEC for appendiceal or colorectal cancer is not associated with decreased survival, and when considering decreased costs, may optimize resource utilization.

Lung Surveillance Strategy for High-Grade Soft Tissue Sarcomas: Chest X-Ray or CT Scan?

BACKGROUND: Given the propensity for lung metastases, National Comprehensive Cancer Network guidelines recommend lung surveillance with either chest x-ray (CXR) or CT in high-grade soft tissue sarcoma. Considering survival, diagnostic sensitivity, and cost, the optimal modality is unknown. METHODS: The US Sarcoma Collaborative database (2000 to 2016) was reviewed for patients who underwent resection of a primary high-grade soft tissue sarcoma. Primary end point was overall survival (OS). Cost analysis was performed. RESULTS: Among 909 patients, 83% had truncal/extremity and 17% had retroperitoneal tumors. Recurrence occurred in 48%, of which 54% were lung metastases. Lung surveillance was performed with CT in 80% and CXR in 20%. Both groups were clinically similar, although CT patients had more retroperitoneal tumors and recurrences. Regardless of modality, 85% to 90% of lung metastases were detected within the first 2 years with a similar re-intervention rate. When considering age, tumor size, location, margin status, and receipt of radiation, lung metastasis was independently associated with worse OS (hazard ratio 4.26; p < 0.01) and imaging modality was not (hazard ratio 1.01; p = 0.97). Chest x-ray patients did not have an inferior 5-year OS rate compared with CT (71% vs 60%; p < 0.01). When analyzing patients in whom no lung metastases were detected, both cohorts had a similar 5-year OS rate (73% vs 74%; p = 0.42), suggesting CXR was not missing clinically relevant lung nodules. When adhering to a guideline-specified protocol for 2018 projected 4,406 cases, surveillance with CXR for 5 years results in savings of $5 million to $8 million/year to the US healthcare system. CONCLUSIONS: In this large multicenter study, lung surveillance with CXR did not result in worse overall survival compared with CT. With considerable savings, a CXR-based protocol can optimize resource use for lung surveillance in high-grade soft tissue sarcoma; prospective trials are needed.

Visual acuity, oncologic, and toxicity outcomes with 103Pd vs. 125I plaque treatment for choroidal melanoma.

PURPOSE: To evaluate outcomes of choroidal melanoma patients treated with 125I or 103Pd plaque brachytherapy. METHODS AND MATERIALS: From 1993 to 2012, our institution treated 160 patients with 103Pd (56.1%) and 125 patients with 125I (43.9%) plaque brachytherapy. Tumor outcomes, visual acuity (VA), and toxicity were compared. Multivariate analyses (MVAs) and propensity score analysis were used to help address differences in baseline characteristics. RESULTS: Median followup was longer for 125I patients, 52.7 vs. 43.5 months (p < 0.01). At baseline, 103Pd patients had lower rates of VA worse than 20/200 (4.4% vs. 16%, p = 0.002), T3-T4 tumors (17.5% vs. 32.8%, p = 0.03), and transpupillary thermotherapy use (3.1% vs. 9.6%, p = 0.001). Both 103Pd and 125I provided >90% 3-year overall survival and >93% 5-year secondary enucleation-free survival. On MVA, radionuclide was not predictive for tumor outcomes. A higher percentage maintained vision better than 20/40 with 103Pd (63% vs. 35%, p = 0.007) at 3 years. MVA demonstrated 103Pd radionuclide (odds ratio [OR]: 2.12, p = 0.028) and tumor height ≤5 mm (OR: 2.78, p = 0.017) were associated with VA better than 20/40. Propensity score analysis matched 23 125I with 107 103Pd patients. 103Pd continued to predict better VA at 3 years (OR: 8.10, p = 0.014). On MVA for the development of VA worse than 20/200 or degree of vision loss, radionuclide was not significant. Lower rates of radiation retinopathy were seen with 103Pd than 125I (3 years: 47.3% vs. 63.9%, p = 0.016), with radionuclide significant in MVA. CONCLUSIONS: Both 125I and 103Pd achieve excellent tumor control. An increased probability of long-term VA better than 20/40 and reduced risk of radiation retinopathy is associated with 103Pd.

Relations Between Residential Proximity to EPA-Designated Toxic Release Sites and Diffuse Large B-Cell Lymphoma Incidence.

OBJECTIVES: Examining the spatial patterns of diffuse large B-cell lymphoma (DLBCL) incidence and residential proximity to toxic release locations may provide insight regarding environmental and sociodemographic risk factors. METHODS: We linked and geocoded cancer incidence data for the period 1999-2008 from the Georgia Comprehensive Cancer Registry with population data from the US Census and the Environmental Protection Agency's Toxics Release Inventory. We conducted cluster analyses and constructed Poisson regression models to assess DLBCL incidence as a function of mean distance to the toxic release sites. RESULTS: In total, 3851 incident DLBCL cases occurred among adults residing in Georgia between 1999 and 2008. Significant focal clustering was observed around 57% of ethylene oxide sites, 5% of benzene sites, 9% of tetrachloroethylene sites, 7% of styrene sites, 10% of formaldehyde sites, 5% of trichloroethylene sites, and 10% of all release sites. Mean distance to sites was significantly associated with DLBCL risk for all chemicals. CONCLUSIONS: Proximity to Toxics Release Inventory sites can be linked to increased DLBCL risk as assessed through focal clustering and Poisson regression, and confirmatory studies using geospatial mapping can aid in further specifying risk factors for DLBCL.

Resolving uncertainty in the spatial relationships between passive benzene exposure and risk of non-Hodgkin lymphoma.

BACKGROUND: Benzene is a known occupational carcinogen associated with increased risk of hematologic cancers, but the relationships between quantity of passive benzene exposure through residential proximity to toxic release sites, duration of exposure, lag time from exposure to cancer development, and lymphoma risk remain unclear. METHODS: We collected release data through the Environmental Protection Agency's Toxics Release Inventory (TRI) from 1989 to 2003, which included location of benzene release sites, years when release occurred, and amount of release. We also collected data on incident cases of non-Hodgkin lymphoma (NHL) from the Georgia Comprehensive Cancer Registry (GCCR) for the years 1999-2008. We constructed distance-decay surrogate exposure metrics and Poisson and negative binomial regression models of NHL incidence to quantify associations between passive exposure to benzene and NHL risk and examined the impact of amount, duration of exposure, and lag time on cancer development. Akaike's information criteria (AIC) were used to determine the scaling factors for benzene dispersion and exposure periods that best predicted NHL risk. RESULTS: Using a range of scaling factors and exposure periods, we found that increased levels of passive benzene exposure were associated with higher risk of NHL. The best fitting model, with a scaling factor of 4 kilometers (km) and exposure period of 1989-1993, showed that higher exposure levels were associated with increased NHL risk (Level 4 (1.1-160kilograms (kg)) vs. Level 1: risk ratio 1.56 [1.44-1.68], Level 5 (>160kg) vs. Level 1: 1.60 [1.48-1.74]). CONCLUSIONS: Higher levels of passive benzene exposure are associated with increased NHL risk across various lag periods. Additional epidemiological studies are needed to refine these models and better quantify the expected total passive benzene exposure in areas surrounding release sites.

Residence proximity to benzene release sites is associated with increased incidence of non-Hodgkin lymphoma.

BACKGROUND: An increased risk of non-Hodgkin lymphoma (NHL) has been observed among individuals with occupational exposure to benzene, but the risk among those living near benzene release sites has not been well described. METHODS: To investigate the spatial patterns of NHL incidence and the association between NHL incidence and distance to benzene release sites, the authors linked and geocoded data on benzene release sites in Georgia from 1988 to 1998 using the Environmental Protection Agency's (EPA) Toxics Release Inventory (TRI), census tract level population statistics, and NHL incidence from the Georgia Comprehensive Cancer Registry (GCCR) from 1999 to 2008. Standardized incidence ratios were mapped by census tract, and a Poisson regression was performed on NHL and NHL subtype incidence data using the mean distance between the tract centroids and release sites as markers of exposure. Cluster analyses were conducted at the global, local, and focal levels. RESULTS: Poisson regression indicated that, for every mile the average distance to benzene release sites increased, there was an expected 0.31% decrease in the risk of NHL. Similar results were observed for all NHL subtypes analyzed. Clusters of NHL were spatially associated with benzene release sites located in metropolitan areas, but not with release sites in other areas of the state. CONCLUSIONS: NHL incidence was significantly higher in census tracts that were closer, on average, to benzene release sites. Additional studies are needed to examine spatial patterns of NHL incidence in other geographic regions and interactions between benzene and other exposures.