Brice Jabo

Sociodemographic disparities in chemotherapy and hematopoietic cell transplantation utilization among adult acute lymphoblastic and acute myeloid leukemia patients

Introduction Identifying sociodemographic disparities in chemotherapy and hematopoietic cell transplantation (HCT) utilization for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) may improve survival for underserved populations. In this study, we incorporate neighborhood socioeconomic status (nSES), marital status, and distance from transplant center with previously studied factors to provide a comprehensive analysis of sociodemographic factors influencing treatments for ALL and AML. Methods Using the California Cancer Registry, we performed a retrospective, population-based study of patients ≥15 years old with ALL (n = 3,221) or AML (n = 10,029) from 2003 through 2012. The effect of age, sex, race/ethnicity, marital status, nSES, and distance from nearest transplant center on receiving no treatment, chemotherapy alone, or chemotherapy then HCT was analyzed. Results No treatment, chemotherapy alone, or chemotherapy then HCT were received by 11%, 75%, and 14% of ALL patients and 36%, 53%, and 11% of AML patients, respectively. For ALL patients ≥60 years old, HCT utilization increased from 5% in 2005 to 9% in 2012 (p = 0.03). For AML patients ≥60 years old, chemotherapy utilization increased from 39% to 58% (p<0.001) and HCT utilization from 5% to 9% from 2005 to 2012 (p<0.001). Covariate-adjusted analysis revealed decreasing relative risk (RR) of chemotherapy with increasing age for both ALL and AML (trend p <0.001). Relative to non-Hispanic whites, lower HCT utilization occurred in Hispanic [ALL, RR = 0.80 (95% CI = 0.65–0.98); AML, RR = 0.86 (95% CI = 0.75–0.99)] and non-Hispanic black patients [ALL, RR = 0.40 (95% CI = 0.18–0.89); AML, RR = 0.60 (95% CI = 0.44–0.83)]. Compared to married patients, never married patients had a lower RR of receiving chemotherapy [ALL, RR = 0.96 (95% CI = 0.92–0.99); AML, RR = 0.94 (95% CI = 0.90–0.98)] or HCT [ALL, RR = 0.58 (95% CI = 0.47–0.71); AML, RR = 0.80 (95% CI = 0.70–0.90)]. Lower nSES quintiles predicted lower chemotherapy and HCT utilization for both ALL and AML (trend p <0.001). Conclusions Older age, lower nSES, and being unmarried predicted lower utilization of chemotherapy and HCT among ALL and AML patients whereas having Hispanic or black race/ethnicity predicted lower rates of HCT. Addressing these disparities may increase utilization of curative therapies in underserved acute leukemia populations.

Association of Primary Tumor Site With Mortality in Patients Receiving Bevacizumab and Cetuximab for Metastatic Colorectal Cancer

Importance Biologic therapy (BT) (eg, bevacizumab or cetuximab) is increasingly used to treat metastatic colorectal cancer (mCRC). Recent investigations have suggested that right- or left-sided primary tumor origin affects survival and response to BT. Objective To evaluate the association of tumor origin with mortality in a diverse population-based data set of patients receiving systemic chemotherapy (SC) and bevacizumab or cetuximab for mCRC. Design, Setting, and Participants This population-based nonconcurrent cohort study of statewide California Cancer Registry data included all patients aged 40 to 85 years diagnosed with mCRC and treated with SC only or SC plus bevacizumab or cetuximab from January 1, 2004, through December 31, 2014. Patients were stratified by tumor origin in the left vs right sides. Interventions Treatment with SC or SC plus bevacizumab or cetuximab. Main Outcomes and Measures Mortality hazards by tumor origin (right vs left sides) were assessed for patients receiving SC alone or SC plus bevacizumab or cetuximab. Subgroup analysis for patients with wild-type KRAS tumors was also performed. Results A total of 11 905 patients with mCRC (6713 men [56.4%] and 5192 women [43.6%]; mean [SD] age, 60.0 [10.9] years) were eligible for the study. Among these, 4632 patients received SC and BT. Compared with SC alone, SC plus bevacizumab reduced mortality among patients with right- and left-sided mCRC, whereas SC plus cetuximab reduced mortality only among patients with left-sided tumors and was associated with significantly higher mortality for right-sided tumors (hazard ratio [HR], 1.31; 95% CI, 1.14-1.51; P < .001). Among patients treated with SC plus BT, right-sided tumor origin was associated with higher mortality among patients receiving bevacizumab (HR, 1.31; 95% CI, 1.25-1.36; P < .001) and cetuximab (HR, 1.88; 95% CI, 1.68-2.12; P < .001) BT, compared with left-sided tumor origin. In patients with wild-type KRAS tumors (n = 668), cetuximab was associated with reduced mortality among only patients with left-sided mCRC compared with bevacizumab (HR, 0.75; 95% CI, 0.63-0.90; P = .002), whereas patients with right-sided mCRC had more than double the mortality compared with those with left-sided mCRC (HR, 2.44; 95% CI, 1.83-3.25, P < .001). Conclusions and Relevance Primary tumor site is associated with response to BT in mCRC. Right-sided primary tumor location is associated with higher mortality regardless of BT type. In patients with wild-type KRAS tumors, treatment with cetuximab benefited only those with left-sided mCRC and was associated with significantly poorer survival among those with right-sided mCRC. Our results underscore the importance of stratification by tumor site for current treatment guidelines and future clinical trials.

C1 Lateral Mass Displacement and Transverse Atlantal Ligament Failure in Jefferson's Fracture: A Biomechanical Study of the “Rule of Spence”

BACKGROUND Jeffersons fracture, first described in 1927, represents a bursting fracture of the C1 ring with lateral displacement of the lateral masses. It has been determined that if the total lateral mass displacement (LMD) exceeds 6.9 mm, there is high likelihood of transverse atlantal ligament (TAL) rupture, and if LMD is less than 5.7 mm TAL injury is unlikely. Several recent radiographic studies have questioned the accuracy and validity of the “rule of Spence” and it lacks biomechanical support. OBJECTIVE To determine the amount of LMD necessary for TAL failure using modern biomechanical techniques. METHODS Using a universal material testing machine, cadaveric TALs were stretched laterally until failure. A high‐resolution, high‐speed camera was utilized to measure the displacement of the lateral masses upon TAL failure. RESULTS Eleven cadaveric specimens were tested (n = 11). The average LMD upon TAL failure was 3.2 mm (±1.2 mm). The average force required to cause failure of the TAL was 242 N (±82 N). From our data analysis, if LMD exceeds 3.8 mm, there is high probability of TAL failure. CONCLUSION Our findings suggest that although the rule of Spence is a conceptually valid measure of TAL integrity, TAL failure occurs at a significantly lower value than previously reported (P < .001). Based on our literature review and findings, LMD is not a reliable independent indicator for TAL failure and should be used as an adjunctive tool to magnetic resonance imaging rather an absolute rule.

Role of lymph node ratio in selection of adjuvant treatment (chemotherapy vs . chemoradiation) in patients with resected gastric cancer

Background Recent randomized controlled trials have failed to show a survival difference between adjuvant chemotherapy (CT) and adjuvant chemoradiotherapy (CRT) in patients with resected gastric cancer (GC). However, a subset of patients with lymph node (LN) positive disease may still benefit from CRT. Additional evidence is needed to help guide physicians in identifying patients in whom CRT should be considered. Our objective was then to compare survival outcomes based on lymph node ratio (LNR) (ratio of metastatic to harvested LNs) for patients with gastric and gastroesophageal junction (GEJ) adenocarcinoma treated with surgery and either CT or CRT. Methods This retrospective population-based study used California Cancer Registry (CCR) data from 2004 to 2013. It included 1,493 patients diagnosed with stage IB-III gastric/GEJ adenocarcinoma and treated with CT or CRT following total or partial gastrectomy. Overall survival (OS) was the primary outcome and GC-specific survival was secondary. Mortality hazards ratios (HR) for these outcomes were computed using propensity score weighted Cox regression models, stratified by LNR strata categories as 0%, 1-9%, 10-25% and >25%. Results Out of 1,493 patients that met inclusion criteria, 462 were treated with CT while 1,031 received CRT. Median follow-up for all subjects was 76 months and median survival was 54 months for CRT and 35 for the CT cohort, P<0.001. Compared to CT, CRT was associated with improved survival among patients with LNR of 10-25% [HR =0.62 (95% CI, 0.46-0.83)] and >25% [HR =0.67 (95% CI, 0.56-0.80)]. Similar findings were observed for GC-specific survival and for analyses limited to patients that had at least 15 LNs evaluated. Conclusions LNR appears to be a simple and readily available measure that could be used in treatment planning for resected GC. CRT offers significant survival advantage over CT among patients with high LN disease burden (LNR of ≥10%).

Comparison of perioperative chemotherapy with adjuvant chemoradiotherapy for resectable gastric cancer: findings from a population-based study

Background Both perioperative chemotherapy (PC) and adjuvant chemoradiotherapy (CRT) improve survival in resectable gastric cancer; however, these treatments have never been formally compared. Our objective was to evaluate treatment trends and compare survival outcomes for gastric cancer patients treated with surgery and either PC or CRT. Methods We performed a retrospective population-based cohort study between 2007 through 2013 using California Cancer Registry data. Patients diagnosed with stage IB-III gastric adenocarcinoma and treated with total or partial gastrectomy were eligible for this study. Based on the type of treatment received, patients were grouped into surgery-only, PC, or CRT. Primary and secondary outcomes were overall survival (OS) and gastric cancer-specific survival (GCCS) respectively. Mortality hazards ratios (HRs) for each of these outcomes were computed using propensity score weighted and covariate-adjusted Cox regression models, stratified by clinical node status. Results Of 2,146 patients who underwent surgical resection, 1,067 had surgery-only, while 771 and 308 received PC or CRT, respectively. Median OS was 25, 33, and 52 months for surgery-only, PC, and CRT, respectively; P<0.001. Overall, patients treated with PC had significantly poorer survival compared to CRT (HR =1.45; 95% CI: 1.22-1.73). PC was also associated with higher mortality in patients with signet ring histology (HR =1.66; 95% CI: 1.21-2.28) and clinical node negative cancer (HR =1.85; 95% CI: 1.32-2.60). Survival was not different between PC vs. CRT in clinical node positive patients (HR =1.29; 95% CI: 0.84-2.08). Of note, the percentage of patients receiving PC increased from 17.5% in 2007-2008, to 41.5% in 2013-2014; P<0.001. Conclusions Despite the rapid adoption of PC, overall, CRT is associated with better survival than PC. Specifically, clinical node negative and signet ring histology patients had better survival when treated with CRT compared to PC. Based on these findings, we recommend against indiscriminate adoption of PC and consideration for CRT over PC in clinical node negative patients.

Incidence of implantable Collamer lens–induced cataract

OBJECTIVE Although the literature on the implantable Collamer lens (ICL) suggests an increasing rate of anterior subcapsular cataract (ASC) development with increasing age and decreasing anterior chamber depth (ACD), the exact correlation is not known. We performed a retrospective observation study of 1653 eyes and calculated the incidence of ICL removal with cataract extraction and intraocular lens placement (CE-IOL) as a result of ASC, in correlation to patients age and ACD. DESIGN Retrospective observation study. SETTING The Gimbel Eye Centre, Calgary, Alberta, Canada. METHODS We analyzed ICL V4 model (Visian ICL; STAAR Surgical, Monrovia, CA) implanted in 1653 eyes with myopia from 2000 to 2012 at the Gimbel Eye Centre, Calgary. Myopic patients aged 19 years and older with no history of cataracts were included. The rate of ICL removal with cataract extraction was calculated. Parameters such as age, sex, refractive sphere, refractive cylinder, length of follow-up, and ACD were collected. Cataract-free survival with comparison of FDA and non-FDA cohorts was conducted using Kaplan-Meier survival curves with the log-rank test. In addition, covariates adjusted hazards ratios and 95% confidence intervals were calculated using Cox regression. RESULTS Of the 1653 eyes included in this study, a total of 46 eyes underwent ICL removal with CE-IOL. The length of follow-up varied between 2 and 14 years. CONCLUSIONS This retrospective study demonstrated that the rate of developing ASCs positively correlated with age and negatively correlated with ACD.

High-Risk Stage II Colon Cancer: Not All Risks Are Created Equal

IntroductionAdjuvant chemotherapy is recommended in patients with stage II colon cancer with high-risk features (HRF). However, there is no quantification of the amount of risk conferred by each HRF or the overall survival (OS) benefit gained by chemotherapy based on the risk factor.ObjectiveTo assess survival benefits associated with adjuvant chemotherapy among stage II colon cancer patients having one or more HRF [T4 tumors, less than 12 lymph nodes examined (< 12LN), positive margins, high-grade tumor, perineural invasion (PNI), and lymphovascular invasion (LVI)].MethodsPatients diagnosed with stage II colon cancer between 2010 and 2013 were identified from California Cancer Registry. Propensity score weighted all-cause mortality hazard ratios (HR) were calculated for combinations of HRF.ResultsA total of 5160 stage II colon cancer patients were identified, of which 2398 had at least one HRF and 510 of 2398 (21%) received adjuvant chemotherapy. Compared with patients with a single HRF, presence of any 2 or ≥ 3 HRF showed increasingly poorer survival [HR 1.42, 95% confidence interval (CI) 1.16–1.73 and HR 2.50, 95% CI 1.96–3.20, respectively]. Chemotherapy was associated with improved overall survival only among patients with T4 as the single HRF (HR 0.51, 95% CI 0.34–0.78) or combinations involving T4 as T4/< 12 LN (HR 0.31, 95% CI 0.11–0.90), T4/high grade (HR 0.26, 95% CI 0.11–0.61), and T4/LVI (HR 0.16, 95% CI 0.04–0.61).ConclusionsNot all high-risk features have similar adverse effects on OS. T4 tumors and their combination with other HRF achieve the most survival benefit with adjuvant therapy. Type and number of high-risk features should be taken into consideration when recommending adjuvant chemotherapy in stage II colon cancer.

Abstract 4827: Does beam radiation treatment of prostate cancer increase rectal cancer risk.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: Prostate cancer (PC) is the most common invasive cancer among US men. The majority of PCs are organ-confined at diagnosis and are candidates for treatment using external beam radiation alone (RAD), prostatectomy alone (SURG), or other protocols. This research was conducted at Loma Linda University using California Cancer Registry (CCR) population-data for 1988-2010. The CCR is part of the Surveillance Epidemiology and End Results (SEER) program. Since 1988, there has been mandatory state-wide reporting of information for all invasive cancers to the CCR including cancer diagnosis and stage, treatment, and demographic characteristics, with greater than 99% case reporting. From 1988-2010, nearly half a million California men were diagnosed with prostate cancer (PC). The majority were organ-confined at diagnosis. Problem: We sought to assess whether RAD treatment of prostate cancer, that exposes peri-rectal tissue to ionizing radiation, was followed by increased risk of rectal cancer, relative to SURG. Methods: We conducted record linkage for all new prostate and rectal (rectum and rectosigmoid junction) cancers in California 1988-2010, identifying men diagnosed with rectal cancer 5+ years following RAD or SURG treatment of organ-confined prostate. Among the men treated with RAD vs SURG, the Cox proportional hazards ratio (HR) for rectal cancer was assessed. Demographic covariates included: age (<50, 50-74, & 75+ years), race/ethnicity as Asian/Other (A-O), non-Hispanic black (NHB), Hispanic (Hisp), and non-Hispanic white (NHW), and socioeconomic status quintiles (1-5 Highest) . Results: There were 194 new rectal cancers among 54,130 PC cases that had been treated with RAD and 254 cases among 69,105 SURG patients. Adjusting for demographic covariates and year of PC diagnosis, the rectal cancer HR with 95% CI for RAD vs. SURG was: HRRAD/SURG=1.58, 95% CI=1.28-1.94. Following are HRs for age (continuous variable) (HRAge=1.02, 95% CI=1.00-1.34) and categories of race/ethnicity (HRA-O/NHW=0.99, 95% CI=0.66-1.49; HRNHB/NHW=1.09, 95% CI=0.75-1.57; HRHisp/NHW=1.07, 95% CI=0.78-1.47); SES (HRSES1/SES5=0.92, 95% CI=0.64-1.34; HRSES2/SES5=1.17, 95% CI=0.87-1.57; HRSES3/SES5=1.20, 95% CI=0.92-1.57; HRSES4/SES5=1.19, 95% CI=0.93-1.54); and PC diagnostic year (continuous variable) (HRYear=0.94, 95%CI=0.92-0.97). Discussion/Conclusions: Findings reveal increased rectal cancer hazards among organ-confined prostate cancer patients treated with RAD, relative to SURG, that is substantially independent of demographic covariates. Treatment of rectal cancer among PC patients treated with RAD is further complicated because they may have already received maximum pelvic RAD dose. Further analyses that seek to distinguish roles of different dose and delivery methods for RAD are ongoing. Citation Format: John W. Morgan, Brice Jabo, Mark Ghamsary, David Bush. Does beam radiation treatment of prostate cancer increase rectal cancer risk. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4827. doi:10.1158/1538-7445.AM2013-4827