S9511: a Southwest Oncology Group phase II study of trimetrexate, 5-fluorouracil, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach.

OBJECTIVE: The primary objective of this trial was to evaluate the response rate for trimetrexate in conjunction with 5-FU and leucovorin (LV) (= TFL) in the treatment of advanced gastric cancer in a phase II, cooperative group setting. METHODS: Patients with locally advanced, unresectable, or metastatic adenocarcinoma of the stomach received trimetrexate 110 mg/m IV over 60 minutes day 1, followed by 5-FU 500 mg/m IV bolus and LV 200 mg/m IV over 60 minutes day 2, followed by oral LV 15 mg every 6 hours x 7 doses, all weekly for 6 weeks followed by 2 weeks of rest, continued until progression. RESULTS: Characteristics for 37 eligible patients: median age 63 (range: 23-83); male/female: 69% of 31%; performance status 0/1/2 15/20/1. The confirmed response rate was 19%, and median overall survival was 6 months. Two patients died as a result of therapy, 1 because of infection without significant neutropenia, and 1 due to perforation of a responding gastric lesion. Seventy-two percent experienced grades 3 and 4 toxicity, most commonly diarrhea, fatigue, and lymphopenia. CONCLUSIONS: This regimen achieves response rates comparable to other 5-FU-based regimens, when used in treatment of incurable gastric cancer. Toxicity appears manageable.

Patient Characteristics and Outcomes of Gastrointestinal Stromal Tumor Patients Undergoing Imatinib Plasma Level Testing

Although gastrointestinal stromal tumor (GIST) is effectively treated with imatinib, there are a number of clinical challenges in the optimal treatment of these patients. The plasma steady-state trough level of imatinib has been proposed to correlate with clinical outcome. Plasma imatinib level may be affected by a number of patient characteristics. Additionally, the ideal plasma trough concentration of imatinib is likely to vary based on the KIT genotype (genotype determines imatinib binding affinity) of the individual patient. Patients’ genotype or plasma imatinib level may influence the type and duration of response that is appreciable by clinical evaluation. The objectives of this study were to determine effects of genotype on the type of response appreciable by current imaging criteria, to determine the distribution of plasma imatinib levels in patients with GIST, to determine factors that correlate with plasma imatinib level, to determine the incremental effects of imatinib dose escalation; and to explore the median plasma levels and outcomes of patients with various KIT mutations. We therefore obtained KIT mutation information and analyzed CT response for size and density measurement of GISTs at baseline and within the first four moths of imatinib treatment. In 126 patients with metastatic/unresectable disease, the KIT genotype of patients’ tumor was significantly associated with unique response characteristics measurable by CT. Furthermore, hepatic and peritoneal metastases differed in their response characteristics. A subgroup of patients with KIT exon 9 mutation, who received higher doses of imatinib and experienced higher trough imatinib levels, experienced improved progression-free survival similar to that of KIT exon 11 patients. Therefore, we have found that imatinib plasma levels were higher in patients with elevated Aspartate amino transferase, were women, were older, or were being treated concomitantly with CYP450 substrate drugs. As expected, CYP450 inducers correlated with a lower plasma imatinib levels in GIST patients. Renal metabolism of imatinib accounts for <10%, so it was not included in the analysis but may affect covariates. Interestingly, there was a trend for low imatinib levels and inferior progression-free survival in patients who had undergone complete gastrectomy. Patients with KIT exon 9 mutation in our cohort received higher imatinib doses, experienced higher trough imatinib levels, and experienced a PFS similar to that of KIT exon 11 patients. In conclusion, imatinib plasma levels are influenced by a number of patient characteristics. The optimal imatinib plasma level for individual patients is not known but is an area of intense investigation. Our study confirms patients with KIT exon 9 mutations benefit from high-dose imatinib and higher trough imatinib levels.

THE ASSOCIATION BETWEEN CANCER-RELATED-FATIGUE, RESPONSE TO FATIGUE TREATMENT, AND CYTOKINES AND THEIR RECEPTORS, IN PATIENTS WITH ADVANCED CANCER

Background: Inflammation is implicated in the development of cancer related fatigue (CRF). However there is limited literature on the mediators of inflammation (namely), cytokines and their receptors, associated with clinically significant fatigue and response to treatment. Methods: We reviewed 37 advanced cancer patients with fatigue (≥4/10), who participated in two Randomized Controlled Trials, of anti-inflammatory agents (Thalidomide and Dexamethasone) for CRF. Responders showed improvement in FACIT-F subscale at the end of study (Day 15). Baseline patient characteristics and symptoms were assessed by FACIT-F, ESAS; serum cytokines [IL-1β and receptor antagonist (IL-1RA), IL-6, IL-6R, TNF-α and sTNF-R1 and R2, IL-8, IL-10, IL-17] levels measured by Luminex. Data were analyzed using principal component analysis (PCA) [reporting cumulative variance (variance) for the first four components] to determine their association with fatigue and response to treatment. Results: Females were 54%. Mean (SD) was as follows for age, 61(14); baseline FACIT (F) scores, 21.4(8.6); ESAS Fatigue item, 6.5(1.9); and FACIT-F change, 6.4(9.7); ESAS (fatigue) change, -2 (2.41). Baseline median in pg/mL for IL-6, TNF-α, IL-1β were 31.9; 18.9; 0.55, respectively. Change in IL-6 negatively correlated with change in FACIT-F scores (p=0.02). Baseline CRF (FACIT-F score) was associated with IL-6, IL-6R and IL-17, Variance = 78% whereas IL-10, IL-1RA, TNF-α and IL-1β were associated with improvement of CRF, Variance=74%. Conversely, IL-6 and IL-8 were associated with no improvement or worsening of CRF, Variance= 93%. Conclusions: Change in IL-6 negatively correlated with change in FACIT-F scores. IL-6, IL-6R and IL-17 are associated with CRF while IL-6 and IL-8 were associated with no improvement of CRF. Further studies are warranted confirm our findings.

Cancer patients' attitudes toward cancer trials

Background. Accurate measurement of attitudes toward participation in cancer treatment trials (CTs) and cancer prevention trials (CPTs) across varied groups could assist health researchers and educators when addressing attitudinal barriers to participation in these trials. ^ Methods. The Attitudes toward Cancer Trials Scales (ACTS) instrument development was based on a conceptual model developed from research literature, clinical practice experience, and empirical testing of items with a sample of 312 respondents. The ACTS contains two scales, the Cancer Trials (CT) scale (4 components; 18 items) and the Cancer Prevention Trials (CPT) scale (3 components; 16 items). Cronbach's alpha values for the CT and CPT scales, respectively, were 0.86 and 0.89. These two scales along with sociodemographic and cancer trial history variables were distributed in a mail survey of former patients of a large cancer research center. The disproportionate stratified probability sampling procedure yielded 925 usable responses (54% response rate). ^ Results. Prevalence of favorable attitudes toward CTs and CPTs was 66% and 69%, respectively. There were no significant differences in mean scale scores by cancer site or gender, but African Americans had more favorable attitudes toward CTs than European Americans. Multiple regression analysis indicated that older age, lower education level, and prior CT participation history were associated with more favorable attitudes toward CTs. Prior CT participation and prior CPT participation were associated with more favorable attitudes toward CPTs. Results also provided evidence of reliability and construct validity for both scales. ^ Conclusions. Middle age, higher education, and European American ethnicity are associated with less positive attitudes about participating in cancer treatment trials. Availability of a psychometrically sound instrument to measure attitudes may facilitate a better understanding decision making regarding participation in CTs and CPTs. It is this author's intention that the ACTS' scales will be used by other investigators to measure attitudes toward CTs and CPTs in various groups of persons, and that the many issues regarding participation in trials might become more explicit. ^

A quality of life subscale for terminally ill cancer patients

A subscale was developed to assess the quality of life of cancer patients with a life expectancy of six months or less. Phase I of this study identified the major concerns of 74 terminally ill cancer patients (19 with breast cancer, 19 with lung cancer, 18 with colorectal cancer, 9 with renal cell cancer, 9 with prostate cancer), 39 family caregivers, and 20 health care professionals. Patients interviewed were being treated at the University of Texas M. D. Anderson Cancer Center or at the Hospice at the Texas Medical Center in Houston. In Phase II, 120 patients (30 with breast cancer, 30 with lung cancer, 30 with colorectal cancer, 15 with prostate cancer, and 15 with renal cell cancer) rated the importance of these concerns for quality of life. Items retained for the subscale were rated as "extremely important" or "very important" by at least 60% of the sample and were reported as being applicable by at least two-thirds of the sample. The 61 concerns that were identified were formatted as a questionnaire for Phase III. In Phase III, 356 patients (89 with breast cancer, 88 with lung cancer, 88 with colorectal cancer, 44 with prostate cancer, and 47 with renal cell cancer) were interviewed to determine the subscale's reliability and sensitivity to change in clinical status. Both factor analysis and item response theory supported the inclusion of the same 35 items for the subscale. Internal consistency reliability was moderate to high for the subscale's domains: spiritual (0.87), existential (0.76), medical care (0.68), symptoms (0.67), social/family (0.66), and emotional (0.61). Test-retest correlation coefficients also were high for the domains: social/family (0.86), emotional (0.83), medical care (0.83), spiritual (0.75), existential (0.75), and symptoms (0.81).^ In addition, concurrent validity was supported by the high correlation between the subscale's symptom domain and symptom items from the European Organization for Research and Treatment of Cancer (EORTC) scale (r = 0.74). Patients' functional status was assessed with the Eastern Cooperative Oncology Group (ECOG) Performance status rating. When ECOG categories were compared to subscale domains, patients who scored lower in functional status had lower scores in the spiritual, existential, social/family, and emotional domains. Patients who scored lower in physical well-being had higher scores in the symptom domain. Patient scores in the medical care domain were similar for each ECOG category. The results of this study support the subscale's use in assessing quality of life and the outcomes of palliative treatment for cancer patients in their last six months of life. ^

Risk, outcomes, and cost of emergency center visits in cancer patients

Cancer is a chronic disease that often necessitates recurrent hospitalizations, a costly pattern of medical care utilization. In chronically ill patients, most readmissions are for treatment of the same condition that caused the preceding hospitalization. There is concern that rather than reducing costs, earlier discharge may shift costs from the initial hospitalization to emergency center visits. ^ This is the first descriptive study to measure the incidence of emergency center visits (ECVs) after hospitalization at The University of M. D. Anderson Cancer Center (UTMDACC), to identify the risk factors for and outcomes of these ECVs, and to compare 30-day all-cause mortality and costs for episodes of care with and without ECVs. ^ We identified all hospitalizations at UTMDACC with admission dates from September 1, 1993 through August 31, 1997 which met inclusion criteria. Data were electronically obtained primarily from UTMDACC's institutional database. Demographic factors, clinical factors, duration of the index hospitalization, method of payment for care, and year of hospitalization study were variables determined for each hospitalization. ^ The overall incidence of ECVs was 18%. Forty-five percent of ECVs resulted in hospital readmission (8% of all hospitalizations). In 1% of ECVs the patient died in the emergency center, and for the remaining 54% of ECVs the patient was discharged home. Risk factors for ECVs were marital status, type of index hospitalization, cancer type, and duration of the index hospitalization. The overall 30-day all-cause mortality rate was 8.6% for hospitalizations with an ECV and 5.3% for those without an ECV. In all subgroups, the 30-day all-cause mortality rate was higher for groups with ECVs than for those without ECVs. The most important factor increasing cost was having an ECV. In all patient subgroups, the cost per episode of care with an ECV was at least 1.9 times the cost per episode without an ECV. ^ The higher costs and poorer outcomes of episodes of care with ECVs and hospital readmissions suggest that interventions to avoid these ECVs or mitigate their costs are needed. Further research is needed to improve understanding of the methodological issues involved in relation to health care issues for cancer patients. ^

The pain experience of elderly hospice patients with cancer

Purpose/objectives. A grounded theory design was used to identify, describe, and generate a theoretical analysis of the pain experience of elderly hospice patients with cancer. ^ Sample. Eleven participants over the age of 65, receiving services from a for-profit hospice were interviewed in their homes. ^ Methods. Broad unstructured face to face audio-taped interviews were transcribed verbatim and analyzed using constant-comparative method of analysis. ^ Findings. Pain was described as a hierarchy of chronic, acute, and psychological pain with psychological pain as the worst. Suffering was the basic social problem of pain. Participants dealt with suffering by the basic social process of enduring. Enduring had two sub-processes, maintaining hope and adjusting. Trusting in a higher being and finding meaning were mechanisms of maintaining hope. Mechanisms of adjusting were dealing with uncertainty, accepting, and minimizing pain. ^ Implications for nursing practice. Nurses need to recognize and value the hard work of enduring to deal with suffering. Assisting elderly hospice patients with cancer to address the sub-processes of enduring and their mechanisms can foster enduring. ^

Cystoscopy and the development of invasive bladder cancer in patients presenting with superficial urinary bladder cancer

The objective of this study was to determine the impact of different follow-up cystoscopy frequencies on time to development of invasive bladder cancer in a cohort of 3,658 eligible patients 65 and older with an initial diagnosis of superficial bladder cancer between 1994 and 1998. Bladder cancer patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database were used as the study population. ^ It was hypothesized that superficial bladder cancer patients receiving less frequent cystoscopy follow-up would develop invasive bladder cancer sooner after initial diagnosis and treatment than patients seen more frequently for cystoscopy follow-up. Cox Proportional Hazard Regression revealed that patients seen for cystoscopy every 3 or more months were 83–89% less likely to develop invasive cancer than patients seen every 1 to 2 months. A comparison of the 2 groups (1 to 2 months vs. 3≥ months) revealed that the 1 to 2 month group may have had more aggressive disease, and they are seen more frequently as a result. ^ These findings suggest that there are two groups of superficial bladder cancer patients: those at high risk of developing invasive bladder cancer and those at low risk. Patients who developed invasive bladder cancer sooner after initial diagnosis and treatment were seen more frequently for cystoscopy follow-up. The recommendation is that cystoscopy should be based on disease status at 3 months. Standardized schedules give all patients the same number of cystoscopies regardless of their risk factors. This could lead to unnecessary cystoscopies in low risk patients, and fewer than optimal cystoscopies in high risk patients. ^

Bayesian dual threshold design with Dirichlet distribution: An alternative way to frequentist multi-stage phase II designs in oncology

Many phase II clinical studies in oncology use two-stage frequentist design such as Simon's optimal design. However, they have a common logistical problem regarding the patient accrual at the interim. Strictly speaking, patient accrual at the end of the first stage may have to be suspended until all patients have events, success or failure. For example, when the study endpoint is six-month progression free survival, patient accrual has to be stopped until all outcomes from stage I is observed. However, study investigators may have concern when accrual is suspended after the first stage due to the loss of accrual momentum during this hiatus. We propose a two-stage phase II design that resolves the patient accrual problem due to an interim analysis, and it can be used as an alternative way to frequentist two-stage phase II studies in oncology. ^

Comprehensive environmental study in high risk areas for cancer patients comparing air and water Aspergillus species samples

Background. Nosocomial invasive aspergillosis (a highly fatal disease) is an increasing problem for immunocompromised patients. Aspergillus spp. can be transmitted via air (most commonly) and by water. ^ The hypothesis for this prospective study was that there is an association between patient occupancy, housekeeping practices, patients, visitors, and Aspergillus spp. loading. Rooms were sampled as not terminally cleaned (dirty) and terminally cleaned (clean). The secondary hypothesis was that Aspergillus spp. positive samples collected from more than one sampling location within the same patient room represent the same isolate. ^ Methods. Between April and October 2004, 2873 environmental samples (713 air, 607 water, 1256 surface and 297 spore traps) were collected in and around 209 “clean” and “dirty” patient rooms in a large cancer center hospital. Water sources included aerosolized water from patient room showerheads, sinks, drains, and toilets. Bioaerosol samples were from the patient room and from the running shower, flushing toilet, and outside the building. The surface samples included sink and shower drains, showerheads, and air grills. Aspergillus spp. positive samples were also sent for PCR, molecular typing (n = 89). ^ Results. All water samples were negative for Aspergillus spp. There were a total of 130 positive culturable samples (5.1%). The predominant species found was Aspergillus niger. Of the positive culturable samples, 106 (14.9%) were air and 24 (3.8%) were surface. There were 147 spore trap samples, and 49.5% were positive for Aspergillus/Penicillum spp. Of the culturable positive samples sent for PCR, 16 were indistinguishable matches. There was no significant relationship between air and water samples and positive samples from the same room. ^ Conclusion. Primarily patients, visitors and staff bring the Aspergillus spp. into the hospital. The high number of A. niger samples suggests the spores are entering the hospital from outdoors. Eliminating the materials brought to the patient floors from the outside, requiring employees, staff, and visitors to wear cover up over their street clothes, and improved cleaning procedures could further reduce positive samples. Mold strains change frequently; it is probably more significant to understand pathogenicity of viable spores than to commit resources on molecular strain testing on environmental samples alone. ^

Activation of dendritic cells from patients with epithelial ovarian cancer

Dendritic cells (DCs) are the most potent antigen-presenting cells for inducing immune responses to tumor cells. Lin−HLA-DR + DC populations in peripheral blood mononuclear cells (PBMCs) and in ascites mononuclear leukocytes (MNLs) of patients with epithelial ovarian cancer (EOC) are phenotypically immature. Lin−HLA-DR + DCs from PBMCs of normal subjects and EOC patients and MNLs from ascites cells of patients were examined for specific cell surface markers or indicators of differentiation or activation. Separating Lin− HLA-DR+ DCs into subsets based on their HLA-DR intensity provided an additional method for identifying the two major lineages of DCs, myeloid and plasmacytoid. The activation potential of these DCs following exposure to the maturation agents CD40 ligand (CD40L) and lipopolysaccharide (LPS) was examined by measurement of IL-12 and IL-10 concentrations in DC culture supernatants in addition to their ability to stimulate allogeneic T cells. DCs from PBMCs of normal subjects and EOC patients and DCs isolated from ascites MNLs of EOC patients were separated into subsets based on CD11c and CD123 cell surface marker expression identifying the major DC types. These subsets were then compared with cells sorted on the basis of HLA-DR intensity. The in vivo behavior of DCs and DC subsets in peripheral blood and ascites following treatment of peritoneal carcinoma patients with the growth factor fins-like tyrosine kinase 3 ligand (Flt3L) was also examined. Increases in proportions and total numbers of DCs from peripheral blood and ascites were associated with increased secretion of IL-12 and IL-10 following in vitro activation of cultured DCs. There were differences between DCs from PBMCs and ascites and between DC subsets in expression of cell surface markers, cytokine profile, and the ability of Lin−HLA-DR + cells to stimulate proliferation of allogeneic T cells from EOC patients. These Lin−HLA-DR+ cells have certain functional properties that suggest that they could have the potential to facilitate an adaptive anti-tumor immune response. ^

Oncologic outcomes in diabetic patients with colon cancer

Type II diabetes mellitus is a growing problem worldwide and although its association with increased cardiovascular morbidity and mortality is well known, its role in the development of cancer is now being further elucidated. Recently, there has been increasing evidence that not only are diabetics more susceptible towards development of particular types of cancer, but also have worse oncologic outcomes. This retrospective chart review investigates whether diabetics with colon cancer have a poorer prognosis than their nondiabetic counterparts. Patients with high risk Stage II and Stage III colon cancer who were diagnosed and/or treated at The University of Texas M.D. Anderson Cancer Center from 1/1/2000 till 12/1/2004 were included in our study. We carried out a survival analysis using Kaplan-Meier method and multivariable analysis to assess differences in outcomes of the two population groups. We found that the decreased overall survival in diabetics did not reach statistical significance but this could be due to a lower event rate in our study. Larger studies are required to investigate this further. ^

Response to chemotherapy, recurrence and survival in advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish BRCA mutations, compared to those without

Objectives. Previous studies have shown a survival advantage in ovarian cancer patients with Ashkenazi-Jewish (AJ) BRCA founder mutations, compared to sporadic ovarian cancer patients. The purpose of this study was to determine if this association exists in ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations. In addition, we sought to account for possible "survival bias" by minimizing any lead time that may exist between diagnosis and genetic testing. ^ Methods. Patients with stage III/IV ovarian, fallopian tube, or primary peritoneal cancer and a non-Ashkenazi Jewish BRCA1 or 2 mutation, seen for genetic testing January 1996-July 2007, were identified from genetics and institutional databases. Medical records were reviewed for clinical factors, including response to initial chemotherapy. Patients with sporadic (non-hereditary) ovarian, fallopian tube, or primary peritoneal cancer, without family history of breast or ovarian cancer, were compared to similar cases, matched by age, stage, year of diagnosis, and vital status at time interval to BRCA testing. When possible, 2 sporadic patients were matched to each BRCA patient. An additional group of unmatched, sporadic ovarian, fallopian tube and primary peritoneal cancer patients was included for a separate analysis. Progression-free (PFS) & overall survival (OS) were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were calculated for variables of interest. Matched pairs were treated as clusters. Stratified log rank test was used to calculate survival data for matched pairs using paired event times. Fisher's exact test, chi-square, and univariate logistic regression were also used for analysis. ^ Results. Forty five advanced-stage ovarian, fallopian tube and primary peritoneal cancer patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations, 86 sporadic-matched and 414 sporadic-unmatched patients were analyzed. Compared to the sporadic-matched and sporadic-unmatched ovarian cancer patients, non-AJ BRCA mutation carriers had longer PFS (17.9 & 13.8 mos. vs. 32.0 mos., HR 1.76 [95% CI 1.13–2.75] & 2.61 [95% CI 1.70–4.00]). In relation to the sporadic- unmatched patients, non-AJ BRCA patients had greater odds of complete response to initial chemotherapy (OR 2.25 [95% CI 1.17–5.41]) and improved OS (37.6 mos. vs. 101.4 mos., HR 2.64 [95% CI 1.49–4.67]). ^ Conclusions. This study demonstrates a significant survival advantage in advanced-stage ovarian cancer patients with non-AJ BRCA mutations, confirming the previous studies in the Jewish population. Our efforts to account for "survival bias," by matching, will continue with collaborative studies. ^

Analysis of prognostic factors for the development of metastases and survival in renal cell carcinoma patients

Introduction and objective. A number of prognostic factors have been reported for predicting survival in patients with renal cell carcinoma. Yet few studies have analyzed the effects of those factors at different stages of the disease process. In this study, different stages of disease progression starting from nephrectomy to metastasis, from metastasis to death, and from evaluation to death were evaluated. ^ Methods. In this retrospective follow-up study, records of 97 deceased renal cell carcinoma (RCC) patients were reviewed between September 2006 to October 2006. Patients with TNM Stage IV disease before nephrectomy or with cancer diagnoses other than RCC were excluded leaving 64 records for analysis. Patient TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were analyzed in relation to time to metastases. Time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from metastases to death. Finally, analysis of laboratory values at time of evaluation, Eastern Cooperative Oncology Group performance status (ECOG), UCLA Integrated Staging System (UISS), time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from evaluation to death. Linear regression and Cox Proportional Hazard (univariate and multivariate) was used for testing significance. Kaplan-Meier Log-Rank test was used to detect any significance between groups at various endpoints. ^ Results. Compared to negative lymph nodes at time of nephrectomy, a single positive lymph node had significantly shorter time to metastasis (p<0.0001). Compared to other histological types, clear cell histology had significant metastasis free survival (p=0.003). Clear cell histology compared to other types (p=0.0002 univariate, p=0.038 multivariate) and time to metastasis with log conversion (p=0.028) significantly affected time from metastasis to death. A greater than one year and greater than two year metastasis free interval, compared to patients that had metastasis before one and two years, had statistically significant survival benefit (p=0.004 and p=0.0318). Time from evaluation to death was affected by greater than one year metastasis free interval (p=0.0459), alcohol consumption (p=0.044), LDH (p=0.006), ECOG performance status (p<0.001), and hemoglobin level (p=0.0092). The UISS risk stratified the patient population in a statistically significant manner for survival (p=0.001). No other factors were found to be significant. ^ Conclusion. Clear cell histology is predictive for both time to metastasis and metastasis to death. Nodal status at time of nephrectomy may predict risk of metastasis. The time interval to metastasis significantly predicts time from metastasis to death and time from evaluation to death. ECOG performance status, and hemoglobin levels predicts survival outcome at evaluation. Finally, UISS appropriately stratifies risk in our population. ^

Role of stress myocardial perfusion scan in pre-operative evaluation of cancer patients undergoing non-cardiac surgery

Background. Cardiac risk assessment in cancer patients has not extensively been studied. We evaluated the role of stress myocardial perfusion imaging (MPI) in predicting cardiovascular outcomes in cancer patients undergoing non-cardiac surgery. ^ Methods. A retrospective chart review was performed on 507 patients who had a MPI from 01/2002 - 03/2003 and underwent non-cardiac surgery. Median follow-up duration was 1.5 years. Cox proportional hazard model was used to determine the time-to-first event. End points included total cardiac events (cardiac death, myocardial infarction (MI) and coronary revascularization), cardiac death, and all cause mortality. ^ Results. Of all 507 MPI studies 146 (29%) were abnormal. There were significant differences in risk factors between normal and abnormal MPI groups. Mean age was 66±11 years, with 60% males and a median follow-up duration of 1.8 years (25th quartile=0.8 years, 75th quartile=2.2 years). The majority of patients had an adenosine stress study (53%), with fewer exercise (28%) and dobutamine stress (16%) studies. In the total group there were 39 total cardiac events, 31 cardiac deaths, and 223 all cause mortality events during the study. Univariate predictors of total cardiac events included CAD (p=0.005), previous MI (p=0.005), use of beta blockers (p=0.002), and not receiving chemotherapy (p=0.012). Similarly, the univariate predictors of cardiac death included previous MI (p=0.019) and use of beta blockers (p=0.003). In the multivariate model for total cardiac events, age at surgery (HR 1.04, p=0.030), use of beta blockers (HR 2.46; p=0.011), dobutamine MPI (HR 3.08; p=0.018) and low EF (HR 0.97; p=0.02) were significant predictors of worse outcomes. In the multivariate model for predictors of cardiac death, beta blocker use (HR=2.74; p=0.017) and low EF (HR=0.95; p<0.003) were predictors of cardiac death. The only univariate MPI predictor of total cardiac events was scar severity (p=0.005). While MPI predictors of cardiac death were scar severity (p= 0.001) and ischemia severity (p=0.02). ^ Conclusions. Stress MPI is a useful tool in predicting long term outcomes in cancer patients undergoing surgery. Ejection fraction and severity of myocardial scar are important factors determining long term outcomes in this group.^